Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR.

Diabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome; is increasing at a very fast pace among every group of the population worldwide. It arises due to the inability of the body to produce enough insulin (the hormone responsible for controlling blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy, neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase (DPP-IV) inhibitors (gliptins) hold a significant place.

Parkinson's Disease: A Progressive Neurodegenerative Disorder and Structure-Activity Relationship of MAO Inhibitor Scaffolds as an Important Therapeutic Regimen.

Parkinson's disease is considered an advancing neurodegenerative disorder with unknown causes, and its association with some risk factors, including aging, family history, and exposure to chemicals, makes it the second most common occurring neurodegenerative disorder throughout the world with increasing prevalence. Parkinson's disease is associated with slow movement, rigidity, tremors, imbalance, depression, anxiety, cognitive impairment, orthostasis, hyperhidrosis, sleep disorders, pain, and sensory disturbances. In recent decades, there has been a rise in research on the development of effective and potential therapies for the treatment of Parkinson's disease.

Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors.

A new series of quinoxaline derivatives possessing the hydrazone moiety were designed, synthesized, and screened for in-vitro anti-inflammatory activity by the bovine serum albumin (BSA) denaturation technique, and for antioxidant activity, by the (2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The synthesized compounds were also tested for p38α mitogen-activated protein (MAP) kinase inhibition. The in-vivo anti-inflammatory activity was assessed by the carrageenan-induced rat paw edema inhibition method.

Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents.

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, β-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine.

Evaluation of Antidiabetic Effect of Luteolin in STZ Induced Diabetic Rats: Molecular Docking, Molecular Dynamics, In Vitro and In Vivo Studies.

Despite the existence of modern antidiabetic medications, diabetes still affects millions of individuals worldwide, with a high death and disability rate. There has been a concerted search for alternative natural medicinal agents; luteolin (LUT), a polyphenolic molecule, might be a good choice, both because of its efficacy and because of it having fewer side effects, compared to conventional medicines. This study aims to explore the antidiabetic potential of LUT in diabetic rats, induced by streptozotocin (STZ; 50 mg/kg b.

Pyrazole scaffold-based derivatives: A glimpse of α-glucosidase inhibitory activity, SAR, and route of synthesis.

The α-glucosidase is a validated target to develop drugs for treating type 2 diabetes mellitus. The existing α-glucosidase inhibitors have certain shortcomings related to side effects and route of synthesis. Accordingly, it is inevitable to develop new chemical templates as α-glucosidase inhibitors.

Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics.

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research.

Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study.

Pharmacophore modelling, 3 D QSAR modelling, virtual screening, and molecular dynamics study, all-in-one combination were employed successfully design and develop an alpha-glucosidase inhibitor. To explain the structural prerequisites of biologically active components, 3 D-QSAR models were generated using the selected best hypothesis (AARRR) for compounds 55 included in the model C. The selection of 3 D-QSAR models showed that the Gaussian steric characteristic is crucial to alpha glucosidase's inhibitory potential.

L. and COVID-19: A Glance at The Anti-COVID-19 Chemical Constituents, Clinical Trials, Inventions, and Patent Literature.

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. L.

An Updated and Focused Review on Heterocyclic Inhibitors for SARSCoV and SARS-CoV-2 3CL.

Background: SARS-CoV and SARS-CoV-2 are exceedingly contagious and typically result in major respiratory illnesses (acute respiratory syndrome). The public health is facing enormous challenges across all the nations due to these newly emerging pathogens. Reliable and systematic examination of SARS-CoV and COVID-19 will assist in identifying infectious persons accurately.

Withdrawn: Biomarkers in Disease Diagnosis and the Role of LC-MS and NMR: A Review.

Unlabelled: The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Design. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.

Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors.

Some ()-3-(3-(4-(benzyloxy)phenyl)-1-phenyl-1-pyrazol-4-yl)-1-phenylprop-2-en-1-one conjugates - were designed; synthesized; characterized by H, C NMR, and ESI-MS; and evaluated for tubulin polymerization inhibitory activity and in vitro cytotoxicity against breast (MCF-7), cervical (SiHa), and prostate (PC-3) cancer cell lines, as well as a normal cell line (HEK-293T). The compounds were also tested to determine their binding modes at the colchicine-binding site of tubulin protein (PDB ID-3E22), for in silico ADME prediction, for bioactivity study, and for PASS prediction studies. Among all the synthesized conjugates, compound exhibited excellent cytotoxicity with an IC value of 2.

Recent developments made in the assessment of the antidiabetic potential of gymnema species - From 2016 to 2020.

Background: In traditional herbal medicine, the Gymnema species has been well known for various therapeutic activities such as anti-diabetic, anti-inflammatory, anti-bacterial, anti-arthritic, anti-hyperlipidemic, cytotoxic, and immunostimulatory activities. This review is an effort to analyse all the recent studies done to explore the anti-diabetic potential of traditional Gymnema species. Gymnema sylvestre (Retz.

Sirolimus loaded chitosan functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles for potential treatment of age-related macular degeneration.

The usefulness of sirolimus (SIR) in the treatment of diseases that involve retinal degeneration like age-related macular degeneration (AMD) has been well documented. However, the problem still remains probably owing to the peculiar environment of the eye and/or unfavourable physiochemical profile of SIR. In the present work, we aimed to fabricate sirolimus loaded PLGA nanoparticles (SIR-PLGA-NP) and chitosan decorated PLGA nanoparticles (SIR-CH-PLGA-NP) to be administered via non-invasive subconjunctival route.

Current Status of Novel Pyridine Fused Derivatives as Anticancer Agents: An Insight into Future Perspectives and Structure Activity Relationship (SAR).

Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease.

Antitumor and hepatoprotective effect of Cuscuta reflexa Roxb. in a murine model of colon cancer.

Ethnopharmacological Relevance: Cuscuta reflexa Roxb. (C. reflexa) is a well-known traditional herbal plant, with numerous inherent therapeutic potentials including anticancer, antitumor, antibacterial, analgesic, anthelmintic, laxative and others.

Innovations and Patent Trends in the Development of USFDA Approved Protein Kinase Inhibitors in the Last Two Decades.

Protein kinase inhibitors (PKIs) are important therapeutic agents. As of 31 May 2021, the United States Food and Drug Administration (USFDA) has approved 70 PKIs. Most of the PKIs are employed to treat cancer and inflammatory diseases.

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice.

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3',4',7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties.

Development of a Validated Bioanalytical UPLC-MS/MS Method for Quantification of Neratinib: A Recent Application to Pharmacokinetic Studies in Rat Plasma.

Neratinib, a tyrosine kinase inhibitor, was very recently approved by USFDA in 2017 as an anticancer drug to treat of HER2 positive breast cancers. The present work provides an account on the development of a validated bioanalytical UPLC-MS/MS method for quantification of neratinib and internal standard (imatinib) in rat plasma and tissue homogenates. A UPLC having a 100 mm C18 column (1.

GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus.

Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India.

An analysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α.

Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IMP)α directly and averts interaction with IMPβ1, leading to the prevention of nuclear localization signal (NLS) recognition.

Effect of augmented glycation in mobilization of plasma free fatty acids in type 2 diabetes mellitus.

Background And Aims: Type 2 Diabetes Mellitus (T2DM) is known to be associated with an increase in total plasma free fatty acid (FFA) concentration. The present study was conducted to determine the changes in plasma fatty acids at different levels of glycation in type 2 diabetes mellitus.

Methods: The study involved 50 subjects having different levels of glycation (HbA1c 4.

Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015-2019).

The over expression of EGFR has been recognized as the driver mechanism in the occurrence and progression of carcinomas such as lung cancer, breast cancer, pancreatic cancer, etcetera. EGFR receptor was thus established as an important target for the management of solid tumors. The occurrence of resistance caused as a result of mutations in EGFR has presented a formidable challenge in the discovery of novel inhibitors of EGFR.

Recent advancement in the discovery and development of anti-epileptic biomolecules: An insight into structure activity relationship and Docking.

Although there have been many advancements in scientific research and development, the cause of epilepsy still remains an open challenge. In spite of high throughput research in the field of anti-epileptic drugs, efficacy void is still prevalent before the researchers. Researchers have persistently been exploring all the possibilities to curb undesirable side effects of the anti-epileptic drugs or looking for a more substantial approach to diminish or cure epilepsy.