Quantum mechanical, virtual screening, molecular docking, molecular dynamics, ADME and antimicrobial activity studies of some new indole-hydrazone derivatives as potent agents against E. faecalis.

In this study, a new series of indole-5-carbaldehyde hydrazone derivative compounds were designed, synthesized, and their antimicrobial activities were determined by the microdilution method, and the in vitro cytotoxic effects on Beas-2b cell lines were investigated by MTT assay. When the activity results were examined, 5i12 showed promising activity against E. faecalis with MIC: 2 µg/mL compared to ampicillin, gentamicin, and vancomycin, although the antimicrobial activities of the indole derivatives were generally weaker than those of the standard drugs. Compounds showed no cytotoxic activity on the A549, MCF-7, and Beas-2b cell lines. Molecular docking studies were performed on 15 different proteins to understand the mechanism of 5i12's good antimicrobial action against E. faecalis, and it was concluded that the compounds interacted with FabH, not enough other protein structures. Molecular dynamics simulations were performed to investigate the protein-ligand stability of the most active compound against E. faecalis. The RMSD value of 5i12 varied between 0.02 and 0.16 nm during the MD simulation. The apoprotein peaked at 0.55 nm at the beginning of the simulation and stabilized below 0.5 nm. The theoretical ADME profiles of all compounds were calculated and found to comply with Lipinski and other limiting rules. In addition, some theoretical quantum parameters (HOMO-LUMO) of compounds, and both MEP analysis and geometric optimization analysis for 5i12 were calculated using the 6-311 G (d,p) base set and DFT/B3LYP theory, and the results were visualized. Communicated by Ramaswamy H. Sarma.

Antimicrobial and antiproliferative activity studies of some new quinoline-3-carbaldehyde hydrazone derivatives.

In this study, a total of 22 piece quinoline-3-carbaldehyde hydrazone derivative compounds were designed and synthesized, 2 of which were not original, their antimicrobial activities were determined with microdilution method and their in vitro cytotoxic effect was investigated in MCF-7 and A549 cells by MTT assay. When the activity results are examined, although the antimicrobial effects of quinoline derivatives, in general, are weaker than standard drugs; 3q5 and 3q6 against MRSA showed promising activity with MIC:16 µg/ml compared to reference drugs. Compounds generally showed weaker cytotoxic activity on the A549 and MCF-7 cell line. 3q12, 3q17 and 3q22 at 100 µM reduced cell viability to 59.28%, 76.24% and 72.92% on A549 cells, respectively. Compound 3q6, one of the most effective compounds against MRSA, formed a 2.10 Å long hydrogen bond between the quinoline nitrogen and ARG132 in the DNA topoisomerase IV active site (PDB: 3FV5). Theoretical ADME profiles of all compounds comply with Lipinski and other limiting rules. In addition, MEP analysis of 3q6, geometric optimization and molecular reactivity analysis were calculated with the 6-311G (d,p) base set DFT/B3LYP theory, and ΔE = ELUMO-EHOMO, which is a measure of the stable structure of the molecule, was calculated as 0.13377 for 3q6 and had the most stable electronic structure among all compounds.

Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents.

A series of novel polyhalogenated 2-phenylbenzimidazoles have been synthesized and evaluated for in vitro antistaphylococcal activity against drug-resistant bacterial strains (methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. Certain compounds inhibit bacterial growth perfectly. 11 was active than vancomycin (0.78 µg/mL) with the lowest MIC values with 0.19 µg/mL against methicillin-resistant Staphylococcus aureus, 8 and 35 exhibited best inhibitory activity against vancomycin-resistant Enterococcus faecium (1.56 µg/mL). The mechanism of action for this class of compounds appears to be different than clinically used antibiotics. These polyhalogenated benzimidazoles have potential for further investigation as a new class of potent anti-methicillin-resistant Staphylococcus aureus and anti-vancomycin-resistant Enterococcus faecium agents.