Exploring Inhibition Mechanisms in Wildtype and T315I BCR-ABL1: An In Silico Approach Integrating Virtual Screening, MD Simulations, and MM-GBSA Analysis.

The BCR-ABL tyrosine kinase which is responsible for the pathogenesis of chronic myeloid leukemia (CML), has emerged as a promising therapeutic target. To address this issue, we employed a comprehensive computational approach integrating virtual screening, molecular dynamics (MD) simulations, and MM-GBSA (Molecular Mechanics/Generalized Born Surface Area) analysis to identify potential inhibitors and elucidate their binding mechanisms. Initially, virtual screening was conducted on 994 compounds from the ZINC database and, these compounds were docked against wildtype and T315I mutant ABL1 for the Type I and Type II ABL1 kinase inhibition mechanisms.

Design, synthesis, molecular modeling, in vitro evaluation of novel piperidine-containing hydrazone derivatives as cholinesterase inhibitors.

In an effort to develop new and effective therapeutic agents for Alzheimer's disease, a series of hydrazone derivatives bearing piperidine rings have been designed and synthesized. The chemical structures of the compounds were characterized by various spectroscopic techniques. In vitro antioxidant and cholinesterase activities of the compounds were evaluated.

Development of new chiral 1,2,4-triazole-3-thiones and 1,3,4-thiadiazoles with promising in vivo anticonvulsant activity targeting GABAergic system and voltage-gated sodium channels (VGSCs).

Antiepileptic drugs (AEDs) are used in the treatment of epilepsy, a neurodegenerative disease characterized by recurrent and untriggered seizures that aim to prevent seizures as a symptomatic treatment. However, they still have significant side effects as well as drug resistance. In recent years, especially 1,3,4-thiadiazoles and 1,2,4-triazoles have attracted attention in preclinical and clinical studies as important drug candidates owing to their anticonvulsant properties.

Discovery of New Dual-Target Agents Against PPAR-γ and α-Glucosidase Enzymes with Molecular Modeling Methods: Molecular Docking, Molecular Dynamic Simulations, and MM/PBSA Analysis.

Type 2 diabetes mellitus (T2DM) has become a serious public health problem both in our country and worldwide, being the most prevalent type of diabetes. The combined use of drugs in the treatment of T2DM leads to serious side effects, including gastrointestinal problems, liver toxicity, hypoglycemia, and treatment costs. Hence, there has been a growing emphasis on drugs that demonstrate dual interactions.

Synthesis, Antimicrobial Activities, and Molecular Modeling Studies of Agents for the Sortase A Enzyme.

Sortase A (SrtA) is an attractive target for developing new anti-infective drugs that aim to interfere with essential virulence mechanisms, such as adhesion to host cells and biofilm formation. Herein, twenty hydroxy, nitro, bromo, fluoro, and methoxy substituted chalcone compounds were synthesized, antimicrobial activities and molecular modeling strategies against the SrtA enzyme were investigated. The most active compounds were found to be T2, T4, and T19 against Streptococcus mutans (S.

Design, Synthesis, Pharmacological Activities, Structure-Activity Relationship, and In Silico Studies of Novel 5-Substituted-2-(morpholinoimino)-thiazolidin-4-ones.

This study is aimed to synthesize morpholine- and thiazolidine-based novel 5-(substituted)benzylidene)-2-(morpholinoimino)-3-phenylthiazolidin-4-ones (-) and characterized by molecular spectroscopy. The synthesized compounds were subjected to antioxidant activity with anticholinesterase, tyrosinase, and urease inhibition activities and evaluated the structure-activity relationship (SAR) of enzyme inhibition activities. Compound was found to be the most active antioxidant.

Design, synthesis, and enzyme inhibition evaluation of some novel Mono- and Di--β-D-Glycopyranosyl Chalcone analogues with molecular docking studies.

In this study, some novel mono- and di--β-D-glycopyranosyl chalcone analogs were designed, synthesized, and characterized. The chalcone derivatives were synthesized with good yields by base-catalyzed Claisen-Schmidt condensation in EtOH solution. Then these chalcones were reacted with TAGBr (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide) in dry acetone under the anhydrous condition at 0-5 °C.

Design, in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives.

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas (1-16) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives (17-32).

Synthesis and evaluation of the antioxidant and anti-tyrosinase activities of thiazolyl hydrazone derivatives and their application in the anti-browning of fresh-cut potato.

Tyrosinase is a key enzyme in the biosynthesis of melanin, which is responsible for the browning of foods as well as many skin disorders. In order to develop new anti-browning agents with dual antioxidant and anti-tyrosinase capacities, a series of 30 thiazolyl hydrazone derivatives were synthesized. Among the molecules prepared, 6 and 30 were found to be the most potent tyrosinase inhibitors with IC values ​​comparable to that of kojic acid.

Investigation of the antimicrobial activities of various antimicrobial agents on Streptococcus Mutans Sortase A through computer-aided drug design (CADD) approaches.

Background And Objective: Tooth decay is a common chronic disease that causes pain, tooth loss, malnutrition, anxiety and significantly affects half of the world's population. Streptococcus mutans (S.mutans), is considered the main pathogen causing tooth decay.