Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents.

In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.

Quinoline-based Schiff bases as possible antidiabetic agents: ligand-based pharmacophore modeling, 3D QSAR, docking, and molecular dynamics simulations study.

α-Glucosidase enzyme inhibition is a legitimate approach to combat type 2 diabetes mellitus as it manages to control postprandial hyperglycemia. In this pursuit, a literature search identified quinoline-based molecules as potential α-glucosidase inhibitors. Thus our intended approach is to identify pharmacophoric features responsible for the α-glucosidase inhibition. This was achieved by performing, ligand-based pharmacophore modeling, 3D QSAR model development, pharmacophore-based screening of a rationally designed quinoline-based benzohydrazide Schiff base library, identifying, synthesizing and characterizing molecules (6a-6j) by IR, (1H and 13C) NMR, and mass studies. Further, these molecules were evaluated for α-glucosidase and α-amylase inhibitory potential. Compound 6c was found to inhibit α-glucosidase enzyme with an IC50 value of 12.95 ± 2.35 µM. Similarly, compound 6b was found to have an IC50 value of 19.37 ± 0.96 µM as compared to acarbose (IC50: 32.63 ± 1.07 µM); the inhibitory kinetics of compounds 6b and 6c revealed a competitive type of inhibition; the inhibitory effect can be attributed to its mapped pharmacophoric feature and model validation with a survival score of 5.0697 and vector score of 0.9552. The QSAR model showed a strong correlation with an R 2 value of 0.96. All the compounds (6a-6j) showed no toxicity in L929 cell lines by the MTT assay method. Further, the binding orientation and stability of the molecules were assessed using molecular docking studies and MD trajectory analysis. The energy profile of the molecules with protein as a complex and molecules alone was evaluated using MM/GBSA and DFT calculations, respectively; finally, the pharmacokinetic profile was computed using ADMET analysis.

Design, synthesis, molecular dynamics simulation, MM/GBSA studies and kinesin spindle protein inhibitory evaluation of some 4-aminoquinoline hybrids.

The discovery of novel chemotherapeutic agents is always challenging for researchers in industry and academia. Among the recent promising anticancer therapeutic targets, an important modulatory factor in mitosis is the expression of the kinesin family motor protein (Eg5). In terms of chemotherapy treatment, mitosis has gained significant attention due to its role as one of the biological processes that can be intervened in it. This study was undertaken to design, synthesise and evaluation of 4-aminoquinoline hybrid compounds as potential Eg5 inhibitors. Based on data collected from Malachite green and steady state ATPase assays, it has been determined that compounds such as 6c, 6d, 6g, and 6h are sensitive to Eg5 inhibition. In special mention, compounds 4 and 6c showed promising inhibitory activity in Malachite green assay with IC50 values of 2.32 ± 0.23 µM and 1.97 ± 0.23 µM respectively. Compound 4 showed favourable inhibitory potential Steady state ATPase Assay with IC50 value of 5.39 ± 1.39 µM. We performed molecular docking, MM/GBSA calculations, and molecular dynamic simulations to evaluate the interactions between ligands and the binding site of the kinesin spindle protein to evaluate the functional consequences of these interactions. As a result of these findings, it can be concluded that these 4-amioquinoline Schiff's base hybrids may prove to be promising candidates for development as novel inhibitors of Eg5. Further in-vivo research in this area is required.

Synthesis, molecular docking and ADME studies of thiazole-thiazolidinedione hybrids as antimicrobial agents.

New thiazole-thiazolidinedione hybrids (5a-k) were efficiently synthesized and evaluated for their in-vitro antimicrobial activity against four fungal and bacterial strains. The chemical structures of the compounds were elucidated by FTIR, 1H NMR, and 13C NMR spectral data. Most of the synthesized compounds were sensitive against gram positive, gram negative bacterial and fungal strains. Among the synthesized molecules, compounds 5h, and 5i exhibited promising inhibitory activity against all selected fungal strains and gram positive bacteria namely, Staphylococcus aureus, and Enterococcus faecalis. The molecular docking results predicted that the thiazole-thiazolidinedione derivatives bind to the active site protein ATP-binding pocket from E. coli, S. aureus and C. albicans with good interaction energy scores. Ct-DNA was used to evaluate the binding interactions of the selected compounds by means of absorption spectroscopy. To further characterize the drug-likeness and ADME properties were calculated using the Qikprop, the result of present study suggests that thiazole-thiazolidinedione hybrid could be an interesting approach for the design of new antimicrobial agents.Communicated by Ramaswamy H. Sarma.