Journal of computer-aided molecular design

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0920-654X1622002FebJournal of computer-aided molecular designJ Comput Aided Mol DesFlexible docking under pharmacophore type constraints.129149129-49FLEXX-PHARM, an extended version of the flexible docking tool FLEXX, allows the incorporation of information about important characteristics of protein-ligand binding modes into a docking calculation. This information is introduced as a simple set of constraints derived from receptor-based type pharmacophore features. The constraints are determined by selected FLEXX interactions and inclusion volumes in the receptor active site. They guide the docking process to produce a set of docking solutions with particular properties. By applying a series of look-ahead checks during the flexible construction of ligand fragments within the active site, FLEXX-PHARM determines which partially built docking solutions can potentially obey the constraints. Solutions that will not obey the constraints are deleted as early as possible, often decreasing the calculation time and enabling new docking solutions to emerge. FLEXX-PHARM was evaluated on various individual protein-ligand complexes where the top docking solutions generated by FLEXX had high root mean square deviations (RMSD) from the experimentally observed binding modes. FLEXX-PHARM showed an improvement in the RMSD of the top solutions in most cases, along with a reduction in run time. We also tested FLEXX-PHARM as a database screening tool on a small dataset of molecules for three target proteins. In two cases, FLEXX-PHARM missed one or two of the active molecules due to the constraints selected. However, in general FLEXX-PHARM maintained or improved the enrichment shown with FLEXX, while completing the screen in considerably less run time.HindleSally ASAFraunhofer Institute for Algorithms and Scientific Computing, Schloss Birlinghoven, Sankt Augustin, Germany. hindle@biosolveit.deRareyMatthiasMBuningChristianCLengaueThomasTengJournal ArticleResearch Support, Non-U.S. Gov't

NetherlandsJ Comput Aided Mol Des87104250920-654X0LigandsEC 1.5.1.3Tetrahydrofolate DehydrogenaseEC 3.4.24.27ThermolysinEC 4.2.1.1Carbonic AnhydrasesIMAlgorithmsBinding SitesCarbonic AnhydraseschemistryComputer SimulationDrug DesignDrug Evaluation, PreclinicalLigandsModels, MolecularProtein BindingSoftwareTetrahydrofolate DehydrogenasechemistryThermolysinchemistry20028221002003326402002822100ppublish1218802210.1023/a:1016399411208J Comput Aided Mol Des. 1998 Sep;12(5):471-909834908J Med Chem. 1989 Aug;32(8):1895-9052502631Nucleic Acids Res. 2000 Jan 1;28(1):235-4210592235Curr Opin Drug Discov Devel. 2001 May;4(3):301-711560062J Chem Inf Comput Sci. 1998 Mar-Apr;38(2):220-329538519J Mol Biol. 1996 May 31;259(1):175-2018648645J Comput Aided Mol Des. 1995 Oct;9(5):381-958594156J Comput Aided Mol Des. 1994 Jun;8(3):243-567964925J Comput Aided Mol Des. 1992 Feb;6(1):61-781583540Curr Opin Struct Biol. 2000 Aug;10(4):401-410981625J Comput Aided Mol Des. 1996 Feb;10(1):41-548786414J Comput Aided Mol Des. 1993 Feb;7(1):83-1028097240J Mol Biol. 1999 Jun 18;289(4):1093-10810369784Proteins. 1999 Nov 1;37(2):228-4110584068Proteins. 2000 Sep 1;40(4):623-3610899786Curr Opin Chem Biol. 2001 Aug;5(4):375-8211470599J Mol Biol. 2001 Apr 27;308(2):377-9511327774J Mol Biol. 1996 Aug 23;261(3):470-898780787J Comput Aided Mol Des. 1997 Jul;11(4):369-849334903Angew Chem Int Ed Engl. 2001 Jan 19;40(2):389-39311180334J Med Chem. 1985 Jul;28(7):849-573892003J Mol Biol. 2000 Jan 14;295(2):337-5610623530trying2...
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3765501MCID_676f085e7aceddc27c0a58df 39724413 39722402 39716714 39715882 39715013 docking "docked"[All Fields] OR "docking"[All Fields] OR "dockings"[All Fields] OR "docks"[All Fields] solutions "pharmaceutical solutions"[Pharmacological Action] OR "solutions"[MeSH Terms] OR "solutions"[All Fields] OR "solution"[All Fields] OR "pharmaceutical solutions"[MeSH Terms] OR ("pharmaceutical"[All Fields] AND "solutions"[All Fields]) OR "pharmaceutical solutions"[All Fields] OR "solutal"[All Fields] OR "solute"[All Fields] OR "solute's"[All Fields] OR "soluted"[All Fields] OR "solutes"[All Fields] OR "solution's"[All Fields] ("docked"[All Fields] OR "docking"[All Fields] OR "dockings"[All Fields] OR "docks"[All Fields]) AND ("pharmaceutical solutions"[Pharmacological Action] OR "solutions"[MeSH Terms] OR "solutions"[All Fields] OR "solution"[All Fields] OR "pharmaceutical solutions"[MeSH Terms] OR ("pharmaceutical"[All Fields] AND "solutions"[All Fields]) OR "pharmaceutical solutions"[All Fields] OR "solutal"[All Fields] OR "solute"[All Fields] OR "solute s"[All Fields] OR "soluted"[All Fields] OR "solutes"[All Fields] OR "solution s"[All Fields]) trying2...
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1582-493428242024DecJournal of cellular and molecular medicineJ Cell Mol MedComprehensive Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Data Unveils Sevoflurane-Induced Neurotoxicity Through SLC7A11-Associated Ferroptosis.e70307e70307e7030710.1111/jcmm.70307Sevoflurane's potential impact on cognitive function and neurodevelopment, especially in susceptible populations such as infants and the elderly, has raised widespread concern. This study focuses on how sevoflurane induces ferroptosis in astrocytes and identifies solute carrier family 7 member 11 (SLC7A11) as a mediator of ferroptosis, providing new insights into sevoflurane-related neurotoxic pathways. We analysed single-cell sequencing (scRNA-seq) data from sevoflurane-exposed mice and control mice, supplemented with bulk RNA-seq data, to assess gene expression alterations. Additionally, pregnant mice were subjected to in vivo experiments, and in vitro studies using U251 astrocytoma cells were conducted to evaluate sevoflurane's neurotoxic effects on offspring, focusing on ferroptosis markers and SLC7A11 expression. Sevoflurane exposure led to learning, memory and behavioural deficits in offspring, associated with decreased SLC7A11 expression and increased signs of ferroptosis. In U251 cells, sevoflurane reduced cell viability, increased reactive oxygen species (ROS) levels and affected the expression of ferroptosis regulatory factors, supporting the hypothesis that sevoflurane induces astrocyte ferroptosis through SLC7A11 modulation. Molecular docking experiments suggest a direct interaction between sevoflurane and SLC7A11. This study provides mechanistic insights into sevoflurane-induced neurotoxicity, emphasising the importance of SLC7A11 in regulating astrocyte ferroptosis. Our findings highlight the potential for targeting ferroptosis pathways to mitigate the adverse effects of sevoflurane anaesthesia.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.HuXiaolanXDepartment of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.ZhangYipingYDepartment of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.GuoLianLDepartment of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.XiaoRenjieRDepartment of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.YuanLinhuiL0009-0004-0635-6072Department of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.LiuFenFDepartment of Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, Jiangxi Medical Center for Critical Public Health Events, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P. R. China.eng20212BAB206048Natural Science Foundation of Jiangxi ProvinceJournal Article

EnglandJ Cell Mol Med1010837771582-183838LVP0K73ASevoflurane0Amino Acid Transport System y+0Reactive Oxygen Species0Slc7a11 protein, mouse0SLC7A11 protein, humanIMSevofluraneadverse effectsFerroptosisdrug effectsgeneticsAnimalsMiceAmino Acid Transport System y+metabolismgeneticsHumansAstrocytesdrug effectsmetabolismFemaleSingle-Cell AnalysisRNA-SeqPregnancyReactive Oxygen SpeciesmetabolismNeurotoxicity SyndromesgeneticspathologyetiologymetabolismCell Line, TumorMolecular Docking SimulationMice, Inbred C57BLCell Survivaldrug effectsSingle-Cell Gene Expression Analysisastrocytecognitive dysfunctionferroptosisneurotoxicitysevofluraneThe authors declare no conflicts of interest.202410292024618202412112024122618172024122618162024122616120241226ppublish3972441310.1111/jcmm.70307PMC11670868Zuo Y., Chang Y., Thirupathi A., Zhou C., and Shi Z., “Prenatal Sevoflurane Exposure: Effects of Iron Metabolic Dysfunction on Offspring Cognition and Potential Mechanism,” International Journal of Developmental Neuroscience 81, no. 1 (2021): 1–9.33259670Liang T. Y., Peng S. Y., Ma M., Li H. Y., Wang Z., and Chen G., “Protective Effects of Sevoflurane in Cerebral Ischemia Reperfusion Injury: A Narrative Review,” Medical Gas Research 11, no. 4 (2021): 152–154.PMC837446034213497Xing W., Zhao J., Liu J., Liu Z., and Chen G., “The Protective Effects of Sevoflurane on Subarachnoid Hemorrhage,” Medical Gas Research 14, no. 1 (2024): 1–5.PMC1071028937721248Ju L. S., Morey T. E., Seubert C. N., and Martynyuk A. E., “Intergenerational Perioperative Neurocognitive Disorder,” Biology 12 (2023): 4.PMC1013581037106766Apai C., Shah R., Tran K., and Pandya Shah S., “Anesthesia and the Developing Brain: A Review of Sevoflurane‐Induced Neurotoxicity in Pediatric Populations,” Clinical Therapeutics 43, no. 4 (2021): 762–778.33674065Gascoigne D. A., Serdyukova N. A., and Aksenov D. P., “Early Development of the GABAergic System and the Associated Risks of Neonatal Anesthesia,” International Journal of Molecular Sciences 22, no. 23 (2021): 12951.PMC865795834884752Huang X., Ying J., Yang D., et al., “The Mechanisms of Sevoflurane‐Induced Neuroinflammation,” Frontiers in Aging Neuroscience 13 (2021): 717745.PMC837515334421578Sun M., Xie Z., Zhang J., and Leng Y., “Mechanistic Insight Into Sevoflurane‐Associated Developmental Neurotoxicity,” Cell Biology and Toxicology 38, no. 6 (2022): 927–943.PMC975093634766256Zhang L., Cheng Y., Xue Z., et al., “Sevoflurane Impairs m6A‐Mediated mRNA Translation and Leads to Fine Motor and Cognitive Deficits,” Cell Biology and Toxicology 38, no. 2 (2022): 347–369.33928466Chang E., Wang Y., Zhu R., et al., “General Anesthetic Action Profile on the Human Prefrontal Cortex Cells Through Comprehensive Single‐Cell RNA‐Seq Analysis,” iScience 26, no. 4 (2023): 106534.PMC1013091237123239Song S. Y., Peng K., Meng X. W., et al., “Single‐Nucleus Atlas of Sevoflurane‐Induced Hippocampal Cell Type‐ and Sex‐Specific Effects During Development in Mice,” Anesthesiology 138, no. 5 (2023): 477–495.36752736Zhao B. J., Song S. Y., Zhao W. M., et al., “The Effect of Sevoflurane Exposure on Cell‐Type‐Specific Changes in the Prefrontal Cortex in Young Mice,” Journal of Neurochemistry 168 (2024): 1080–1096.38317263Wang Y., Cao X., Yang C., et al., “Ferroptosis and Immunosenescence in Colorectal Cancer,” Seminars in Cancer Biology 106‐107 (2024): 156–165.39419366Wu J., Yang J. J., Cao Y., et al., “Iron Overload Contributes to General Anaesthesia‐Induced Neurotoxicity and Cognitive Deficits,” Journal of Neuroinflammation 17, no. 1 (2020): 110.PMC714990132276637Cheng L., Zhu X., Liu Y., Zhu K., Lin K., and Li F., “ACSL4 Contributes to Sevoflurane‐Induced Ferroptotic Neuronal Death in SH‐SY5Y Cells via the 5' AMP‐Activated Protein Kinase/Mammalian Target of Rapamycin Pathway,” Annals of Translational Medicine's 9, no. 18 (2021): 1454.PMC850673334734006Xu Y., Zhang N., Chen C., et al., “Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4‐CHAC1 Pathway,” Frontiers in Oncology 12 (2022): 859621.PMC896956635372041Butler A., Hoffman P., Smibert P., Papalexi E., and Satija R., “Integrating Single‐Cell Transcriptomic Data Across Different Conditions, Technologies, and Species,” Nature Biotechnology 36, no. 5 (2018): 411–420.PMC670074429608179Yu G., Wang L. G., Han Y., and He Q. Y., “clusterProfiler: An R Package for Comparing Biological Themes Among Gene Clusters,” OMICS 16, no. 5 (2012): 284–287.PMC333937922455463Liao W., Xu J., Li B., Ruan Y., Li T., and Liu J., “Deciphering the Roles of Metformin in Alzheimer's Disease: A Snapshot,” Frontiers in Pharmacology 12 (2021): 728315.PMC882906235153733Du M. R., Gao Q. Y., Liu C. L., Bai L. Y., Li T., and Wei F. L., “Exploring the Pharmacological Potential of Metformin for Neurodegenerative Diseases,” Frontiers in Aging Neuroscience 14 (2022): 838173.PMC908734135557834Ning P., Luo A., Mu X., Xu Y., and Li T., “Exploring the Dual Character of Metformin in Alzheimer's Disease,” Neuropharmacology 207 (2022): 108966.35077762Liu T., Bai M., Liu M., et al., “Novel Synergistic Mechanism of 11‐Keto‐β‐Boswellic Acid and Z‐Guggulsterone on Ischemic Stroke Revealed by Single‐Cell Transcriptomics,” Pharmacological Research 193 (2023): 106803.37230158Shi L., Zhang R., Li T., et al., “Decreased miR‐132 Plays a Crucial Role in Diabetic Encephalopathy by Regulating the GSK‐3β/Tau Pathway,” Aging (Albany NY) 13, no. 3 (2020): 4590–4604.PMC790621233406505Liu P. C., Yao W., Chen X. Y., et al., “Parabrachial Nucleus Astrocytes Regulate Wakefulness and Isoflurane Anesthesia in Mice,” Frontiers in Pharmacology 13 (2022): 991238.PMC988044236712675Fu H., Zhou J., Li S., et al., “Isoflurane Impairs Olfaction by Increasing Neuronal Activity in the Olfactory Bulb,” Acta Physiologica 239, no. 1 (2023): e14009.37330999Lin S. S., Zhou B., Chen B. J., et al., “Electroacupuncture Prevents Astrocyte Atrophy to Alleviate Depression,” Cell Death & Disease 14, no. 5 (2023): 343.PMC1022707537248211Yi R., Wang H., Deng C., et al., “Dihydroartemisinin Initiates Ferroptosis in Glioblastoma Through GPX4 Inhibition,” Bioscience Reports 40, no. 6 (2020): BSR20193314.PMC731344332452511Park M. W., Cha H. W., Kim J., et al., “NOX4 Promotes Ferroptosis of Astrocytes by Oxidative Stress‐Induced Lipid Peroxidation via the Impairment of Mitochondrial Metabolism in Alzheimer's Diseases,” Redox Biology 41 (2021): 101947.PMC802777333774476Zhang W., Ding L., Chen H., et al., “Cntnap4 Partial Deficiency Exacerbates α‐Synuclein Pathology Through Astrocyte‐Microglia C3‐C3aR Pathway,” Cell Death & Disease 14, no. 4 (2023): 285.PMC1012267537087484Tang H., He K., Zhao K., et al., “Protective Effects of Hinokitiol on Neuronal Ferroptosis by Activating the Keap1/Nrf2/HO‐1 Pathway in Traumatic Brain Injury,” Journal of Neurotrauma 41, no. 5–6 (2024): 734–750.37962273Dai Y. and Hu L., “HSPB1 Overexpression Improves Hypoxic‐Ischemic Brain Damage by Attenuating Ferroptosis in Rats Through Promoting G6PD Expression,” Journal of Neurophysiology 128, no. 6 (2022): 1507–1517.36321738Liu H., Zhang T. A., Zhang W. Y., Huang S. R., Hu Y., and Sun J., “Rhein Attenuates Cerebral Ischemia‐Reperfusion Injury via Inhibition of Ferroptosis Through NRF2/SLC7A11/GPX4 Pathway,” Experimental Neurology 369 (2023): 114541.37714424Liang P., Zhang X., Zhang Y., et al., “Neurotoxic A1 Astrocytes Promote Neuronal Ferroptosis via CXCL10/CXCR3 Axis in Epilepsy,” Free Radical Biology & Medicine 195 (2023): 329–342.36610561Li M., Zhang J., Jiang L., et al., “Neuroprotective Effects of Morroniside From Cornus officinalis Sieb. Et Zucc Against Parkinson's Disease via Inhibiting Oxidative Stress and Ferroptosis,” BMC Complementary Medicine and Therapies 23, no. 1 (2023): 218.PMC1031449137393274Zheng J., Fang Y., Zhang M., et al., “Mechanisms of Ferroptosis in Hypoxic‐Ischemic Brain Damage in Neonatal Rats,” Experimental Neurology 372 (2024): 114641.380652313972240220241226

1879-12982024Dec23ChemosphereChemosphereMarine microalgae - mediated biodegradation of polystyrene microplastics: Insights from enzymatic and molecular docking studies.14402414402410.1016/j.chemosphere.2024.144024S0045-6535(24)02932-1Biodegradation of microplastics (MPs) through microalgal strains would be of eco-friendly approach for significant pollution abatement. Polystyrene (PS) is a major contaminant in the marine environment; however studies on marine microalgal degradation of PS MPs have been very limited. In the present study, six marine microalgal strains viz. Picochlorum maculatum, Dunaliella salina, Amphora sp., Navicula sp., Synechocystis sp. and Limnospira indica were investigated for their ability to degrade PS MPs for the incubation period of 45 days. Results from weight reduction, ATR-FTIR, SEM, and molecular docking analysis confirmed that microalgae formed biofilms on PS MPs, causing structural changes, and laccase-driven enzymatic breakdown. A maximum weight loss of 23.2 ± 0.21% and a minimum of 11.3 ± 0.026% were caused by the colonized microalgae Synechocystis sp. and Amphora sp. respectively. The study indicated that a higher reduction rate was observed in the Synechocystis sp. treated PS MPs with a rate of 0.0058 g/day and a lower half-life of 119.34 days. SEM analysis showed that microalgae caused pits, erosion, and damage to the PS film. ATR-FTIR confirmed the chemical modifications and proved biodegradation. Laccase enzyme activity was higher in Synechocystis sp., and molecular docking showed the laccase interaction with the derivatives of PS, elucidating the breakdown process. This study highlights the potential of microalgae for eco-friendly microplastic degradation and paves the way for future research on the by-products of this process. Exploring the ecological impact of by-products and optimizing scalable methods can further enhance the sustainability and practical applications of this promising solution.Copyright © 2024. Published by Elsevier Ltd.GowthamiAyyasamyADepartment of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India.MarjukMohammed SyedMSDepartment of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India.PerumalSanthanamSDepartment of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India. Electronic address: santhanamcopepod@gmail.com.ThirumuruganRamasamyRDepartment of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India.MuralisankarThirunavukkarasuTDepartment of Zoology, School of Life Sciences, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India.PerumalPachiappanPDepartment of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India.engJournal Article20241223

EnglandChemosphere03206570045-6535IMBiodegradationMarine PollutionMicroalgaeMicroplasticPolystyreneDeclaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.20241025202412220241222202412266202024122662020241226111aheadofprint3972240210.1016/j.chemosphere.2024.144024S0045-6535(24)02932-13971671420241224

1879-00032024Dec21International journal of biological macromoleculesInt J Biol MacromolExploration of the micellization behavior of sodium dodecyl sulfate in aqueous solution of gastric enzyme pepsin: Assessment of the consequences of sodium electrolytes and temperature.13899013899010.1016/j.ijbiomac.2024.138990S0141-8130(24)09801-5This study explores the interactions between pepsin and sodium dodecyl sulfate (SDS) using conductometric analysis and molecular docking to deepen our understanding of the role of pepsin. Conductometric studies were conducted to examine the micellization behavior of SDS in aqueous solutions of various sodium electrolytes (NaBr, Na₂SO₄, Na₃PO₄, and CH₃COONa) at temperatures ranging from 300.55 K to 320.55 K in 5 K increments. The critical micelle concentration (CMC) of the SDS-pepsin system was influenced by pepsin concentration, electrolyte type, and temperature. Pepsin was found to inhibit SDS micellization, increasing the CMC, while electrolytes promoted micellization, decreasing the CMC. Thermodynamic parameters-Gibbs free energy (∆G_m⁰), enthalpy (∆H_m⁰), and entropy (∆S_m⁰)-were analyzed to identify the driving forces behind micellization. The negative ∆G_m⁰ indicated spontaneous aggregation, with ∆H_m⁰ and ∆S_m⁰ suggesting hydrophobic and electrostatic interactions. Molecular docking further confirmed these interactions, revealing binding between the hydrophobic tail of SDS and nonpolar binding pocket of pepsin at the interdomain cleft. These findings provide insights into surfactant-enzyme interactions, with potential applications in biochemistry, pharmacology, and food science.Copyright © 2024. Published by Elsevier B.V.KabirShahanazSDepartment of Chemistry, Jashore University of Science and Technology, Jashore 7408, Bangladesh.HossainMd Al AminMAADepartment of Chemistry, Jashore University of Science and Technology, Jashore 7408, Bangladesh.JahanIsratIDepartment of Chemistry, Jashore University of Science and Technology, Jashore 7408, Bangladesh. Electronic address: i.jahan@just.edu.bd.AhmedBulbulBDepartment of Chemistry, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.MalikAjamaluddinADepartment of Biochemistry, Collage of Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.GoniMd AbdulMADepartment of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117, USA.HoqueMd AnamulMADepartment of Chemistry, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.Anis-Ul-HaqueK MKMDepartment of Chemistry, Jashore University of Science and Technology, Jashore 7408, Bangladesh. Electronic address: a.haque@just.edu.bd.engJournal Article20241221

NetherlandsInt J Biol Macromol79095780141-8130IMMolecular dockingPepsin proteinProtein-surfactant interactionDeclaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.20241026202412320241217202412246202024122462020241224145aheadofprint3971671410.1016/j.ijbiomac.2024.138990S0141-8130(24)09801-53971588220241223

1432-19122024Dec23Naunyn-Schmiedeberg's archives of pharmacologyNaunyn Schmiedebergs Arch PharmacolTherapeutic potential of 3-acetyl coumarin against polycystic ovarian syndrome induced by letrozole using female rats.10.1007/s00210-024-03720-5Polycystic ovarian syndrome is a heterogeneous endocrine disorder characterized by ovarian cysts, anovulation, endocrine variations, which includes oligo-amenorrhea along with associated subfertility and hyperandrogenism manifested as acne, hirsutism, and male-pattern alopecia. Coumarins are fused benzene and pyrone ring systems that exhibit a wide spectrum of bioactivities. This study aimed to investigate the effects of 3-acetyl coumarin (3-AC) on polycystic ovarian syndrome in female rats. Acute oral toxicity conducted according to OECD guidelines 425 (a test conducted in scenarios where there is information indicating that the test material is non-toxic) exhibited no mortality. In vitro DPPH assay demonstrated anti-oxidant potential of 3-AC. Letrozole, a nonsteroidal aromatase inhibitor was used to induce PCOS (1 mg/kg-21 days). Normal and PCOS control rats were administered a vehicle solution (0.5% CMC), whereas 3-AC (10, 20, and 30 mg/kg) and metformin (300 mg/kg) was administered to treatment groups for 15 days. Vaginal smears were taken to assess estrous cycle. Rats were euthanized at day 37. In vivo analysis included measurement of fasting blood glucose, total-cholesterol, triglycerides, FSH, LH, and testosterone levels. ELISA was used for measurement of inflammatory markers (IL-1β, IL-6, and TNF-α). Oxidative stress markers (SOD, CAT, GSH, MDA, NO) were also evaluated. Expression levels of NF-κB and LHCGR were detected by RT-qPCR. Molecular docking was also performed. One-way analysis of variance was employed followed by Tukey's test for statistical analysis. Treatment with 3-AC led to favorable effects in PCOS rats. Specifically, inflammatory levels, antioxidant status, lipid profile, and glucose concentrations were all improved. These findings suggest that 3-acetyl coumarin (3-AC) may serve as a promising therapeutic agent for alleviating symptoms of PCOS in this animal model.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.ShahbazSalihaSDepartment of Pharmacology, Faculty of Pharmaceutical and Allied Health Sciences, Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan.SharifAliADepartment of Pharmacology, Faculty of Pharmaceutical and Allied Health Sciences, Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan. alisharif.pharmacist@gmail.com.AkhtarBushraBDepartment of Pharmacy, University of Agriculture Faisalabad, Faisalabad, Pakistan.MobasharAishaAFaculty of Pharmacy, The University of Lahore, Lahore, Pakistan.Faculty of Health Sciences, Equator University of Science and Technology, Masaka, Uganda.ShazlyGamal AGADepartment of Pharmaceutics, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia.MetouekelAmiraAUniversity of Technology of Compiègne, EA 4297 TIMR, 60205, Compiègne Cedex, France.BourhiaMohammedMLaboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences, Ibn Zohr University, 80060, Agadir, Morocco. m.bourhia@uiz.ac.ma.engJournal Article20241223

GermanyNaunyn Schmiedebergs Arch Pharmacol03262640028-1298IM3-Acetyl coumarinInflammatory markersLetrozoleOxidative stressPCOSDeclarations. Ethics approval and consent to participate: The study was conducted followed by the approval of the Institutional Animal Ethics Committee. Ethics no. ORIC/LCWU/405 in accordance with the NC3Rs ARRIVE Guidelines, adhere to ethical guidelines of The Basel Declaration, the International Council for Laboratory Animal Science (ICLAS) ethical guidelines, and Directive 2010/63/EU. ARRIVE guidelines: The experimentation was conducted in accordance with applicable laws, and ARRIVE guidelines. Ethical consideration: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.2024101420241282024122402520241224025202412232325aheadofprint3971588210.1007/s00210-024-03720-510.1007/s00210-024-03720-5Abdul Hamid F, Abu MA, Abdul Karim AK, Ahmad MF, Abd Aziz NH, Mohd Kamal DA, Mokhtar MHJB (2022) Sex steroid receptors in polycystic ovary syndrome and endometriosis: insights from laboratory studies to clinical trials. Biomed 10(7):1705Abdulghani M, Hussin AH, Sulaiman SA, Chan KL (2012) The ameliorative effects of Eurycoma longifolia Jack on testosterone-induced reproductive disorders in female rats. Reprod Biol 12(2):247–2552285047410.1016/S1642-431X(12)60089-8Abizadeh M, Novin MG, Amidi F, Ziaei SA, Abdollahifar MA, Nazarian HJRS (2020a) Potential of auraptene in improvement of oocyte maturation, fertilization rate, and inflammation in polycystic ovary syndrome mouse model. Reprod Sci 27(9):1742–17513212439610.1007/s43032-020-00168-9Abizadeh M, Novin MG, Amidi F, Ziaei SA, Abdollahifar MA, Nazarian H (2020b) Potential of auraptene in improvement of oocyte maturation, fertilization rate, and inflammation in polycystic ovary syndrome mouse model. Reprod Sci 27:1742–17513212439610.1007/s43032-020-00168-9Abraham Gnanadass S, Divakar Prabhu Y, Valsala Gopalakrishnan AJAOG (2021) Obstetrics, association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update. Arch Gynecol Obstetr 303:631–64310.1007/s00404-020-05951-2Adashi EYJER (1990) The Potential Relevance of Cytokines to Ovarian Physiology: the Emerging Role of Resident Ovarian Cells of the White Blood Cell Series. Endocr Rev 11(3):454–464222635110.1210/edrv-11-3-454Akhtar MF, Mehal MO, Saleem A, El Askary A, Abdel-Daim MM, Anwar F, Ayaz M, Zeb AJES, Research P (2022) Attenuating effect of Prosopis cineraria against paraquat-induced toxicity in prepubertal mice. Mus Musculus 29(10):15215–15231Akintoye OO, Ajibare AJ, Oriyomi IA, Olofinbiyi BA, Yusuf GO, Afuye DC, Babalola TK, Faturoti OE, Oludipe S, Owoyele VBJLS (2023) Synergistic action of carvedilol and clomiphene in mitigating the behavioral phenotypes of letrozole-model of PCOS rats by modulating the NRF2/NFKB pathway. Life Sci 324:1217373712718310.1016/j.lfs.2023.121737Alam MN, Bristi NJ, Rafiquzzaman M (2013) Review on in vivo and in vitro methods evaluation of antioxidant activity. Saudi Pharm J 21(2):143–1522493613410.1016/j.jsps.2012.05.002Amadi CF, Okolonkwo BN, George-Oparati MI, Odiabara KK (2023) Understanding the relationship between polycystic ovarian syndrome (PCOS) and dyslipidemia. Asian J Biochem Gen Mol Biol 15(3):1–1110.9734/ajbgmb/2023/v15i3333Asif M (2015) Pharmacologically potentials of different substituted coumarin derivatives. Chem Int 1:1–11Azouz AA, Ali SE, Abd-Elsalam RM, Emam SR, Galal MK, Elmosalamy SH, Alsherbiny MA, Hassan BB, Li CG, El Badawy SA (2021) Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect. Chinese Med 16(1):3610.1186/s13020-021-00444-zAzziz RJF (2016) Sterility, introduction: determinants of polycystic ovary syndrome. Fertil Steril 106(1):4–52723862710.1016/j.fertnstert.2016.05.009Balkwill F, Mantovani AJTL (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–5451122968410.1016/S0140-6736(00)04046-0Bansal Y, Sethi P, Bansal G (2013) Coumarin: a potential nucleus for anti-inflammatory molecules. Med Chem Res 22(7):3049–306010.1007/s00044-012-0321-6Basheer M, Bhat AH, Hajam YA, Batiha GE-S, Ataya FS, Fouad D, Rai S (2023) Melatonin as a promising therapeutic intervention for restoring ovarian function in letrozole-induced polycystic ovary syndrome rats. Heliyon 9(11)Böhm EW, Buonfiglio F, Voigt AM, Bachmann P, Safi T, Pfeiffer N, Gericke A (2023) Oxidative stress in the eye and its role in the pathophysiology of ocular diseases. Redox Biol 102967Borges Bubols G, da Rocha Vianna D, Medina-Remon A, von Poser G, Maria Lamuela-Raventos R, Lucia Eifler-Lima V, Cristina Garcia SJMRIMC (2013) The Antioxidant Activity of Coumarins and Flavonoids. Mini Rev Med Chem 13(3):318–334Bril F, Ezeh U, Amiri M, Hatoum S, Pace L, Chen Y-H, Bertrand F, Gower B, Azziz R (2024) Adipose tissue dysfunction in polycystic ovary syndrome. J Clin Endocrinol Metab 109(1):10–2410.1210/clinem/dgad356Bulsara J, Patel P, Soni A, Acharya S (2021) A review: brief insight into polycystic ovarian syndrome. Endocr Metab Sci 3:10008510.1016/j.endmts.2021.100085Consensus on infertility treatment related to polycystic ovary syndrome (2008) Hum Reprod 23 (3):462–77Darabi P, Khazali H, Mehrabani Natanzi M (2020) Therapeutic potentials of the natural plant flavonoid apigenin in polycystic ovary syndrome in rat model: via modulation of pro-inflammatory cytokines and antioxidant activity. Gynecol Endocrinol 36(7):582–5873188839510.1080/09513590.2019.1706084Dhivya C, Dhanalakshmi S, Chitra V, Hawari S (2018) Alleviation of polycystic ovarian syndrome by hydroalcoholic leaf extract of Aegle marmelos (L). Correa in letrozole-induced rat model. Drug Invention Today 10 (7)Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA, Chrousos GPJTIE (2007) Metabolism, pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 18(7):280–2851769253010.1016/j.tem.2007.07.004Ding H, Zhang J, Zhang F, Zhang S, Chen X, Liang W, Xie Q (2021) Resistance to the insulin and elevated level of androgen: a major cause of polycystic ovary syndrome. Front Endocrinol 12:74176410.3389/fendo.2021.741764Dinsdale NL, Crespi BJJEA (2021) Endometriosis and polycystic ovary syndrome are diametric disorders. Evol Appl 14(7):1693–171534295358828800110.1111/eva.13244Eijkemans MJ, Imani B, Mulders AG, Habbema JD, Fauser BC (2003) High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility (WHO 2). Hum Reprod 18(11):2357–23621458588710.1093/humrep/deg459El-Bahya AAZ, Radwanb RA, Gadc MZ, Abdel SMJGJPPS (2018) A closer insight into the role of vitamin D in polycystic ovary syndrome (Pcos). Global J Pharmaceu Sci 6:79–87Emam S, Abd-Elsalam R, Azouz A, Ali S, El Badawy S, Ibrahim M, Hassan B, Issa M, Elmosalamy SJJPP (2021) Linum usitatissimum seeds oil down-regulates mrna expression for the steroidogenic acute regulatory protein and Cyp11A1 genes, ameliorating letrezole-induced polycystic ovarian syndrome in a rat model 72(1)Engmann L, Maslow B, Kaye L, Griffin D, Diluigi A, Schmidt D, Grow D, Nulsen J, Benadiva CJJOOR (2019) Low dose human chorionic gonadotropin administration at the time of gonadotropin releasing-hormone agonist trigger versus 35 h later in women at high risk of developing ovarian hyperstimulation syndrome–a prospective randomized double-blind clinical trial. J Ovarian Res 12(1):1–910.1186/s13048-019-0483-7Faheem M, Jamal SBJL (2020) Science, Identification of Zika virus NS5 novel inhibitors through virtual screening and docking studies. Life Sci 1(1):5–510.37185/LnS.1.1.42Femi-Olabisi JF, Ishola AA, Olujimi FO (2023) Effect of Parquetina nigrescens (Afzel.) Leaves on letrozole-induced PCOS in rats: a molecular insight into its phytoconstituents. Appl Biochem Biotechnol 195(8):4744–47743717175810.1007/s12010-023-04537-3Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DNJCPD (2004) Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities. Curr Pharm Des 10(30):3813–38331557907310.2174/1381612043382710Gao Y, Zou Y, Wu G, Zheng L (2023) Oxidative stress and mitochondrial dysfunction of granulosa cells in polycystic ovarian syndrome. Front Med 10:119374910.3389/fmed.2023.1193749González F, Sia CL, Stanczyk FZ, Blair HE, Krupa MEJE (2012) Hyperandrogenism Exerts an Anti-Inflammatory Effect in Obese Women with Polycystic Ovary Syndrome. Endocr 42:726–73510.1007/s12020-012-9728-6Ha L-X, Li W-X, Du Y-D, Yuan Y-Y, Qu X-X (2022) Tumor necrosis factor alpha level in the uterine fluid of patients with polycystic ovary syndrome and its correlation with clinical parameters. J Inflamm Res 6015–6020Hamza AH, Albishri WM, Alfaris MH (2019) Effect of Vitex agnus-castus plant extract on polycystic ovary syndrome complications in experimental rat model. Asian Pacific J Reprod 8(2):63–6910.4103/2305-0500.254647Heidary M, Yazdanpanahi Z, Dabbaghmanesh MH, Parsanezhad ME, Emamghoreishi M, Akbarzadeh MJJORIMSTOJOIUOMS (2018) Effect of chamomile capsule on lipid-and hormonal-related parameters among women of reproductive age with polycystic ovary syndrome 23Hiam D, Moreno-Asso A, Teede HJ, Laven JS, Stepto NK, Moran LJ, Gibson-Helm MJJOCM (2019) The genetics of polycystic ovary syndrome: an overview of candidate gene systematic reviews and genome-wide association studies. J Clin Med 8(10):160631623391683258310.3390/jcm8101606Huang J-C, Yue Z-P, Yu H-F, Yang Z-Q, Wang Y-S, Guo B (2022) TAZ ameliorates the microglia-mediated inflammatory response via the Nrf2-ROS-NF-κb pathway. Molecular Therapy-Nucleic Acids 28:435–44935505966904386610.1016/j.omtn.2022.03.025Ibrahim YF, Alorabi M, Abdelzaher WY, Toni ND, Thabet K, Hegazy A, Bahaa HA, Batiha GE-S, Welson NN, Morsy MA (2022) Pharmacotherapy, diacerein ameliorates letrozole-induced polycystic ovarian syndrome in rats. Biomed Pharmacother 149:1128703536776910.1016/j.biopha.2022.112870Jungbauer A, Medjakovic S (2014) Phytoestrogens and the metabolic syndrome. J Steroid Biochem Mol Biol 139:277–2892331887910.1016/j.jsbmb.2012.12.009Kaya S, Sütçü R, Cetin ES, Arıdogan BC, Delibaş N, Demirci M (2007) Lipid peroxidation level and antioxidant enzyme activities in the blood of patients with acute and chronic fascioliasis. Int J Infect Dis 11(3):251–2551685994410.1016/j.ijid.2006.05.003Khajouei A, Hosseini E, Abdizadeh T, Kian M, Ghasemi S (2021a) Beneficial effects of minocycline on the ovary of polycystic ovary syndrome mouse model: molecular docking analysis and evaluation of TNF-α, TNFR2, TLR-4 gene expression. J Reprod Immunol 144:1032893361092810.1016/j.jri.2021.103289Khajouei A, Hosseini E, Abdizadeh T, Kian M, Ghasemi S (2021b) Beneficial effects of minocycline on the ovary of polycystic ovary syndrome mouse model: molecular docking analysis and evaluation of TNF-α, TNFR2, TLR-4 gene expression. J Reprod Immunol 144:1032893361092810.1016/j.jri.2021.103289Khan S, Suhagia BN, Prajapati N, Teli D (2024) Design, synthesis and biological evaluation of novel 6-amino-3-phenyl-2H-chromen-2-one derivatives for polycystic ovary syndrome management. ChemistrySelect 9(38):e20240326810.1002/slct.202403268Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Perspective improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8(6):114810.1371/journal.pbio.1000412Kumar TR, Wang Y, Lu N, Matzuk MM (1997) Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 15(2):201–204902085010.1038/ng0297-201Liu LS, Winston JH, Shenoy MM, Song GQ, Chen JD, Pasricha PJ (2008) A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation. Gastroenterology 134(7):2070–20791844810210.1053/j.gastro.2008.02.093Liu Y, Liu H, Li Z, Fan H, Yan X, Liu X, Xuan J, Feng D, Wei X (2021) The release of peripheral immune inflammatory cytokines promote an inflammatory cascade in PCOS patients via altering the follicular microenvironment. Front Immunol 12:68572434079559816544310.3389/fimmu.2021.685724Mcallister JM, Legro RS, Modi BP, Strauss JFJTIE (2015) Metabolism, functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab 26(3):118–12425600292434647010.1016/j.tem.2014.12.004Mihanfar A, Nouri M, Roshangar L, Khadem-Ansari MH (2021) Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome. J Steroid Biochem Mol Biol 213:1059543429809810.1016/j.jsbmb.2021.105954Nallathambi A, Bhargavan R (2019) Regulation of estrous cycle by Cynodon dactylon in letrozole induced polycystic ovarian syndrome in Wistars albino rats. Anat Cell Biol 52:51131949991695268310.5115/acb.19.114Negahdari FM, Gholamnezhad Z, Noshahr ZS, Keshavarzi Z (2021) A comparison between the effect of trans-anethole and metformin on biochemical parameters of polycystic ovary syndrome in rats. Avicenna J Phytomed 11(5):484Nilsson MB, Langley RR, Fidler IJJCR (2005) Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 65(23):10794–1080016322225153411410.1158/0008-5472.CAN-05-0623OECD (2022) Test No. 425: Acute oral toxicity: up-and-down procedureOlaniyi KS, Oniyide AA, Adeyanju OA, Ojulari LS, Omoaghe AO, Olaiya OE (2021) Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS. Toxicol Appl Pharmacol 411:1153813335918210.1016/j.taap.2020.115381Oyebanji OG, Asaolu MF (2020) Assessment of antioxidant status of women with polycystic ovarian syndrome. Asian Pacific J Reprod 9(1):9–1510.4103/2305-0500.275523Pandey V, Singh A, Singh A, Krishna A, Pandey U, Tripathi YB (2016) Role of oxidative stress and low-grade inflammation in letrozole-induced polycystic ovary syndrome in the rat. Reprod Biol 16(1):70–772695275610.1016/j.repbio.2015.12.005Pasquali R (2006) Obesity and androgens: facts and perspectives. Fertil Steril 85(5):1319–13401664737410.1016/j.fertnstert.2005.10.054Patel SK (2011) In In vitro antioxidant activity of coumarin compounds by DPPH, Super oxide and nitric oxide free radical scavenging methodsQu X, Donnelly R (2020) Sex hormone-binding globulin (SHBG) as an early biomarker and therapeutic target in polycystic ovary syndrome. Int J Mol Sci 21(21):819133139661766373810.3390/ijms21218191Reddy PS, Begum N, Mutha S, Bakshi V (2016) Beneficial effect of curcumin in letrozole induced polycystic ovary syndrome. Asian Pac J Reprod 5(2):116–12210.1016/j.apjr.2016.01.006Repaci A, Gambineri A, Pasquali R (2011) The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 335(1):30–412070806410.1016/j.mce.2010.08.002Riasat I, Bakhtiar SM, Faheem M, Jaiswal AK, Naeem M, Khan R, Khan AU, Khalil AAK, Haider A, Junaid MJAN (2022) Application of Pan Genomics towards the Druggability of Clostridium Botulinum 12(11):3237–3249Rodgers RJ, Suturina L, Lizneva D, Davies MJ, Hummitzsch K, Irving-Rodgers HF, Robertson SAJMH (2019) Is polycystic ovary syndrome a 20th century phenomenon? Med Hypotheses 124:31–343079891110.1016/j.mehy.2019.01.019Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J, Calvo M, Bermúdez VJIJORM (2014) Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth 2014Rudic J, Jakovljevic V, Jovic N, Nikolic M, Sretenovic J, Mitrovic S, Bolevich S, Bolevich S, Mitrovic M, Raicevic SJA (2022) Antioxidative Effects of Standardized Aronia Melanocarpa Extract on Reproductive and Metabolic Disturbances in a Rat Model of Polycystic Ovary Syndrome. Antioxidants 11(6):109935739998922011210.3390/antiox11061099Ryu Y, Kim SW, Kim YY, Ku S-YJIJOMS (2019) Animal models for human polycystic ovary syndrome (PCOS) focused on the use of indirect hormonal perturbations: a review of the literature. Int J Mol Sci 20(11):272031163591660035810.3390/ijms20112720Sashidhara KV, Kumar A, Kumar M, Srivastava A, Puri A (2010) Synthesis and antihyperlipidemic activity of novel coumarin bisindole derivatives. Bioorg Med Chem Lett 20(22):6504–65072093274410.1016/j.bmcl.2010.09.055Satpathy L, Dash D, Sahoo P, Anwar T, Parida SP (2020) Quantitation of total protein content in some common edible food sources by lowry protein assay. Lett Appl Nanobiosci 9(3):1275–128310.33263/LIANBS93.12751283Sharif PM, Jabbari P, Razi S, Keshavarz-Fathi M, Rezaei N (2020) Importance of TNF-alpha and its alterations in the development of cancers. Cytokine 130:15506610.1016/j.cyto.2020.155066Shirooie S, Khaledi E, Dehpour AR, Noori T, Khazaei M, Sadeghi F, Sobarzo-Sánchez E (2021) The effect of dapsone in testosterone enanthate-induced polycystic ovary syndrome in rat. J Steroid Biochem Mol Biol 214:1059773442859410.1016/j.jsbmb.2021.105977Shrivastava VK (2022) Turmeric extract alleviates endocrine-metabolic disturbances in letrozole-induced PCOS by increasing adiponectin circulation: a comparison with metformin. Metabolism Open 13:1001603500559610.1016/j.metop.2021.100160Singh H, Singh JV, Bhagat K, Gulati HK, Sanduja M, Kumar N, Kinarivala N, Sharma S (2019) Rational approaches, design strategies, structure activity relationship and mechanistic insights for therapeutic coumarin hybrids. Bioorg Med Chem 27(16):3477–351031255497797083110.1016/j.bmc.2019.06.033Sirotkin AVJTIJOB (2011) Cytokines: signalling molecules controlling ovarian functions. Int J Biochem Cell Biol 43(6):857–8612138250410.1016/j.biocel.2011.03.001Srikrishna D, Godugu C, Dubey PKJMRIMC (2018) A review on pharmacological properties of coumarins. Mini Rev Med Chem 18(2):113–1412748858510.2174/1389557516666160801094919Sun J, Jin C, Wu H, Zhao J, Cui Y, Liu H, Wu L, Shi Y, Zhu B (2013) Effects of electro-acupuncture on ovarian p450arom, P450c17α and mrna expression induced by letrozole in PCOS rats. Plos One 8(11)Taşdemir E, Atmaca M, Yıldırım Y, Bilgin HM, Demirtaş B, Obay BD, Kelle M, Oflazoğlu HDJH, Toxicology E (2017) Influence of coumarin and some coumarin derivatives on serum lipid profiles in carbontetrachloride-exposed rats. Hum Exp Toxicol 36(3):295–3012718518110.1177/0960327116649675Tejada S, Martorell M, Capo X, A Tur J, PonsSureda AAJCTIMC (2017) Coumarin and derivates as lipid lowering agents. Curr Top Med Chem 17(4):391–3982755868210.2174/1568026616666160824102322Tsutsumi R, Webster NJ (2009) GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr J 56(6):729–73719609045430780910.1507/endocrj.K09E-185Unluhizarci K, Karaca Z, Kelestimur F (2021) Role of insulin and insulin resistance in androgen excess disorders. World J Diabetes 12(5):61633995849810797810.4239/wjd.v12.i5.616Vassalli PJAROI (1992) The Pathophysiology of Tumor Necrosis Factors. Annu Rev Immunol 10(1):411–452159099310.1146/annurev.iy.10.040192.002211Vural P, Değirmencioğlu S, Saral NY, Akgül CJEJOO, Gynecology, Biology R (2010) Tumor necrosis factor α (− 308), interleukin-6 (− 174) and interleukin-10 (− 1082) gene polymorphisms in polycystic ovary syndrome. Eur J Obstetr Gynecol Reprod Biol 150(1):61–6510.1016/j.ejogrb.2010.02.010Wadood A, Jamal SB, Riaz M, Mir AJPB (2014) Computational analysis of benzofuran-2-carboxlic acids as potent Pim-1 kinase inhibitors. Pharm Biol 52(9):1170–11782476636410.3109/13880209.2014.880488Walters KA, Allan CM, Handelsman DJJBOR (2012) Rodent models for human polycystic ovary syndrome. Biol Reprod 86(5):149–1-122233733310.1095/biolreprod.111.097808Walters KA, Gilchrist RB, Ledger WL, Teede HJ, Handelsman DJ, Campbell RE (2018) New perspectives on the pathogenesis of PCOS: neuroendocrine origins. Trends Endocrinol Metab 29(12):841–8523019599110.1016/j.tem.2018.08.005Xie Y, Xiao L, Li S (2021) Effects of metformin on reproductive, endocrine, and metabolic characteristics of female offspring in a rat model of letrozole-induced polycystic ovarian syndrome with insulin resistance. Front Endocrinol 12:70159010.3389/fendo.2021.7015903971501320241223

1520-51182024Dec23Journal of agricultural and food chemistryJ Agric Food ChemStructural Feature of Salty/Saltiness-Enhancing Peptides Derived from Coprinus comatus and Their Stability during Subsequent Thermal Treatment and Maillard Reaction.10.1021/acs.jafc.4c10426Through a quantitative analysis of saltiness perception, favorable enzymatic hydrolysis parameters were confirmed for the preparation of saltiness-enhancing peptide mixtures from Coprinus comatus. The enzymatic hydrolysate was fractionated into four fractions (F1-F4) by gel chromatography, with F3 exhibiting the strongest saltiness-enhancing effect (22% increase). LC-MS/MS analysis of F3 identified 36 peptides, and their secondary structures and interactions with the TMC4 receptor were examined through circular dichroism spectroscopy and molecular docking. Molecular docking analysis revealed Asn588, Ser165, Asp5, and Arg168 as key amino acid residues, with the peptide GDNVGF showing the lowest binding energy. Synthetic GDNVGF (0.01%) in 70 mmol/L NaCl enhanced saltiness by 17%. When 0.7% GDNVGF was added to the aqueous solution, its saltiness was equivalent to that of 36.89 mmol/L NaCl, which suggested that GDNVGF functions both as a saltiness-enhancing peptide and a salty peptide. The taste changes of peptides during thermal reactions were further investigated. The thermal stability of Coprinus comatus peptides was good, but their saltiness-enhancing effect slightly reduced due to thermal degradation. The Maillard reaction further diminished this effect, though the umami level remained satisfactory, offering new insights into using Coprinus comatus peptides as low-sodium salt substitutes.SongMingzhouMState Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, P.R. China.ZhouTongTState Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, P.R. China.LiaoQiuhongQInstitute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610299, P.R. China.ZhangFoxinFAnhui Province Key Laboratory of Functional Compound Seasoning, Anhui Qiang Wang Flavouring Food Co., Ltd, Jieshou 236500, Anhui, P.R. China.HussainShahzadSDepartment of Food Science and Nutrition, College of Food and Agriculture, King Saud University, P. O Box 2460, Riyadh 11451, Saudi Arabia.HayatKhizarKDepartment of Food and Animal Sciences, Alabama A&M University, Normal, Alabama 35762, United States.ZhangXiaomingX0000-0002-1673-6026State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, P.R. China.Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610299, P.R. China.HoChi-TangCTDepartment of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey 08901, United States.engJournal Article20241223

United StatesJ Agric Food Chem03747550021-8561IMCoprinus comatusmolecular dockingsaltiness enhancement peptidessecondary structurethermal stability202412232258202412232258202412231243aheadofprint3971501310.1021/acs.jafc.4c10426trying2...
Flexible docking under pharmacophore type constraints. | LitMetric

Flexible docking under pharmacophore type constraints.

Sally A Hindle Matthias Rarey Christian Buning Thomas Lengaue

J Comput Aided Mol Des

Fraunhofer Institute for Algorithms and Scientific Computing, Schloss Birlinghoven, Sankt Augustin, Germany.

Published: February 2002

FLEXX-PHARM, an extended version of the flexible docking tool FLEXX, allows the incorporation of information about important characteristics of protein-ligand binding modes into a docking calculation. This information is introduced as a simple set of constraints derived from receptor-based type pharmacophore features. The constraints are determined by selected FLEXX interactions and inclusion volumes in the receptor active site. They guide the docking process to produce a set of docking solutions with particular properties. By applying a series of look-ahead checks during the flexible construction of ligand fragments within the active site, FLEXX-PHARM determines which partially built docking solutions can potentially obey the constraints. Solutions that will not obey the constraints are deleted as early as possible, often decreasing the calculation time and enabling new docking solutions to emerge. FLEXX-PHARM was evaluated on various individual protein-ligand complexes where the top docking solutions generated by FLEXX had high root mean square deviations (RMSD) from the experimentally observed binding modes. FLEXX-PHARM showed an improvement in the RMSD of the top solutions in most cases, along with a reduction in run time. We also tested FLEXX-PHARM as a database screening tool on a small dataset of molecules for three target proteins. In two cases, FLEXX-PHARM missed one or two of the active molecules due to the constraints selected. However, in general FLEXX-PHARM maintained or improved the enrichment shown with FLEXX, while completing the screen in considerably less run time.

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