New class of thio/semicarbazide-based benzyloxy derivatives as selective class of monoamine oxidase-B inhibitors.

Sixteen thio/semicarbazide-based benzyloxy derivatives (BT1-BT16) were synthesized and evaluated for their inhibitory activities against monoamine oxidases (MAOs). Most compounds showed better inhibitory activity against MAO-B than against MAO-A. BT1, BT3, and BT5 showed the greatest inhibitory activity with an identical IC value of 0.

A literature review on pharmacological aspects, docking studies, and synthetic approaches of quinazoline and quinazolinone derivatives.

Quinazoline and quinazolinone derivatives piqued medicinal chemistry interest in developing novel drug candidates owing to their pharmacological potential. They are important chemicals for the synthesis of a variety of physiologically significant and pharmacologically useful molecules. Quinazoline and quinazolinone derivatives have anticancer, anti-inflammatory, antidiabetic, anticonvulsant, antiviral, and antimicrobial potential.

Enzyme Inhibition Assays for Monoamine Oxidase.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines with two isoforms, namely, MAO-A and MAO-B, in mitochondrial outer membranes. These two types of MAO-A and MAO-B participate in changes in levels of neurotransmitter such as serotonin (5-hydroxytryptamine) and dopamine. Selective MAO-A inhibitors have been targeted for anti-depression treatment, while selective MAO-B inhibitors are targets of therapeutic agents for Alzheimer's disease and Parkinson's disease.

Targeting GABA receptors with chalcone derivative compounds, what is the evidence?

Introduction: In medicinal chemistry, privileged structures have been frequently exploited as a successful template for drug discovery. Common simple scaffolds like chalcone are present in a wide range of naturally occurring chemicals. Chalcone exhibits extensive biological activity and has drawn attention in this context due to its function in the GABA receptor.

Introducing of novel class of pyrano[2,3-]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation.

Microbiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis of a novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, and hydroxyl groups. All new analogs were characterized with full spectroscopic data.

Anti-inflammatory effect of 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole derivatives as p38α inhibitors.

In the present work, the anti-inflammatory effect of 30 compounds containing 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole was investigated. All final target compounds showed significant Inhibitory effect on p38α. P38α is considered one of the key kinases in the inflammatory process due to its regulatory effect on pro-inflammatory mediators.

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and study.

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione , 1,3,4-thiadiazole aryl urea and cyanothiouracil moieties was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, was the most potent showing IC50 of 5.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, , and mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients.

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents.

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (, 1,3,4-thiadiazoles (-, and pyrimidines (-, was preparedand assessed for its potential COX-2 inhibitors. Compared to Celecoxib, compounds and were the most potent derivatives c with a half-maximal inhibitory concentration range of 53-69 nM. Considering COX-2 selectivity index, compounds and were chosen among these most potent derivatives for further investigation.

Screening and Molecular Docking of Bioactive Metabolites of the Red Sea Sponge as Potential Antimicrobial Agents.

Marine sponges create a wide range of bioactive secondary metabolites, as documented throughout the year. Several bioactive secondary metabolites were isolated from different members of species. This study aimed for isolation and structural elucidation of major metabolites in order to investigate their diverse bioactivities such as antimicrobial and anti-biofilm activities.

Effects of radiation exposure on brain health: a state of the art and new challenges.

Good brain health refers to a condition in which a person may fully realize their talents and improve their psychological, emotional, cognitive, and behavioral functioning to cope with life's challenges. Various causes of CNS diseases are now being investigated. Radiation is one of the factors that affects the brain and causes a variety of problems.

Effect of Hydroaloholic Extract of Lour on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats: An and Approach.

One-third of the world population suffer from kidney complications such as acute and chronic renal failure, renal calculi, kidney stones, Fanconi's syndrome and urethritis which doesn't have a proper effective treatment regimen. The current study explores the nephroprotective effect of herbal drug by both and methods. MTT assay was applied to evaluate the nephroprotective effect of leaves extract on HEK 293 cell line.

A meta-analysis showing the effect of surgical site wound infections and associated risk factors in neonatal surgeries.

A meta-analysis was performed to assess the effect of surgical site wound infections and risk factors in neonates undergoing surgery. A systematic literature search up to January 2022 incorporated 17 trials involving 645 neonates who underwent surgery at the beginning of the trial; 198 of them had surgical site wound infections, and 447 were control for neonates. The statistical tools like the dichotomous or continuous method used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the risk factors and influence of surgical site wound infections in neonates undergoing surgery.

A Review on Benzimidazole Scaffolds as Inhibitors of Mycolyl-arabinogalactan-peptidoglycan Complex Biosynthesis.

Background: Tuberculosis is one of the oldest known infectious diseases to mankind, caused by Mycobacterium tuberculosis. Although current treatment using first-line anti-tubercular drugs is proven to be effective, an infection caused by resistant strains, as in multidrug-resistant and extensive drug- resistant tuberculosis is still an impending challenge to treat.

Objective: Our objective is to focus on reporting benzimidazole derivatives that are targeting mycobacterial membrane biosynthesis, particularly the mycobacterial mycolyl-arabinogalactanpeptidoglycan complexes.

Conjugated Dienones from Differently Substituted Cinnamaldehyde as Highly Potent Monoamine Oxidase-B Inhibitors: Synthesis, Biochemistry, and Computational Chemistry.

Fifteen multiconjugated dienones () were synthesized and evaluated to determine their inhibitory activities against monoamine oxidases (MAOs) A and B. All derivatives were found to be potent and highly selective MAO-B inhibitors. Compound , with an IC value of 2.

A meta-analysis comparing efficiency of limb-salvage surgery vs amputation on patients with osteosarcoma treated with neoadjuvant chemotherapy.

Osteogenic sarcoma is the central malignant bone neoplasm affecting the bones of arms and legs and rarely the soft tissues outside the bones. Historically, amputation was the chief surgical technique; currently, the popular standard is limb salvage surgery (LSS), although both procedures' effect on 5-year-event survival, 5-year disease-free survival rates (DFS) and the local recurrence is uncertain. Therefore, this meta-study aimed to establish the relationship between the effect of LSS and amputation in subjects with osteogenic carcinoma.

Trial Approach for Biomedical Products: A Regulatory Perspective.

The modern pharmaceutical industry is transitioning from traditional methods to advanced technologies like artificial intelligence. In the current scenario, continuous efforts are being made to incorporate computational modeling and simulation in drug discovery, development, design, and optimization. With the advancement in technology and modernization, many pharmaceutical companies are approaching in silico trials to develop safe and efficacious medicinal products.

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.

The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate.

The Role of Mitochondrial Genes in Neurodegenerative Disorders.

Mitochondrial disorders are clinically heterogeneous, resulting from nuclear gene and mitochondrial mutations that disturb the mitochondrial functions and dynamics. There is a lack of evidence linking mtDNA mutations to neurodegenerative disorders, mainly due to the absence of noticeable neuropathological lesions in postmortem samples. This review describes various gene mutations in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke.

Ameliorative effect of ethoxylated chalcone-based MAO-B inhibitor on behavioural predictors of haloperidol-induced Parkinsonism in mice: evidence of its antioxidative role against Parkinson's diseases.

Parkinson's disease is a progressive neurodegenerative disorder that affects mostly elderly people above the age of 60. Previously, we have reported that the ethoxylated chalcone derivative (E)-1-(4-ethoxyphenyl)-3-(fluorophenyl)prop-2-en-1-one (E7) showed potent, reversible, and competitive MAO-B inhibition with an IC value of 0.053 μm.

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

Introduction: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance.

Trimethoxy Crown Chalcones as Multifunctional Class of Monoamine Oxidase Enzyme Inhibitors.

Background: Chalcones with methoxy substituent are considered as a promising framework for the inhibition of monoamine oxidase (MAO) enzymes.

Methods: A series of nine trimethoxy substituted chalcones (TMa-TMi) was synthesized and evaluated as a multifunctional class of MAO inhibitors. All the synthesized compounds were investigated for their in vitro MAO inhibition, kinetics, reversibility, blood-brain barrier (BBB) permeation, and cytotoxicity and antioxidant potentials.

Piperazine-substituted chalcones: a new class of MAO-B, AChE, and BACE-1 inhibitors for the treatment of neurological disorders.

Eleven piperazine-containing 1,3-diphenylprop-2-en-1-one derivatives (PC1-PC11) were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with a view toward developing new treatments for neurological disorders. Compounds PC10 and PC11 remarkably inhibited MAO-B with IC values of 0.65 and 0.

An Agathokakological Tale of Δ-THC: Exploration of Possible Biological Targets.

Δ-Tetrahydrocannabinol (Δ-THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system. By interacting with G-proteincoupled receptors CB1 and CB2, Δ-THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release, thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities. Δ-THC effectively suppresses chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis.