Investigation of Novel Quinoline–Thiazole Derivatives as Antimicrobial Agents: In Vitro and In Silico Approaches

Abstract

Infectious diseases are a major concern around the world. Today, it is an urgent need for new chemotherapeutics for infectious diseases. Because of that, our group designed, synthesized, and analyzed 14 new quinoline derivatives endowed with the pharmacophore moiety of fluoroquinolones primarily for their antimicrobial effects. Their cytotoxicity effects were tested against six bacterial and four fungal strains and NIH/3T3 cell line. Additionally, their action mechanisms were evaluated against DNA gyrase and lanosterol 14α-demethylase (LMD). Furthermore, to eliminate the potential side effects, the active compounds were evaluated against the aromatase enzyme. The experimental enzymatic results were evaluated for active compounds’ binding modes using molecular docking and molecular dynamics simulation studies. The results were utilized to clarify the structure–activity relationship (SAR). Finally, compound 4m was the most potent compound for its antifungal activity with low cytotoxicity against healthy cells and fewer possible side effects, while compounds 4j and 4l can be used alone for special patients who are suffering from fungal infections in addition to the primer disease.

Synthesis of new N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE‐1 inhibitory activities

“…MDS method, apoproteins, ligand‐enzyme or ligand‐receptor, etc., it is a useful technique for estimating the time‐dependent stability of systems (Yücel, 2024). As described previously (Dawbaa et al, 2023; Evren, 2022a; Yücel, 2024) the stability of the complex was protected during the entire simulation according to Figure 4a–c.…”

Design and synthesis of phenoxy methyl‐oxadiazole compounds against Alzheimer's disease

“…Because of these indicators, the stability properties (Figure 7a–c) were acceptable as described previously. [ 29,30 ]…”

“…Molecular dynamic simulations included calculations of radius of gyration (Rg), root‐mean‐square fluctuation (RMSF), and root‐mean‐square deviation (RMSD) via the Desmond application. [ 29,49,50 ]…”

“…were acceptable as described previously. [29,30] Figure 7d-f and Video S1 indicated that interactions with Asp74, Phe295, and Phe286 residues have a major role in inhibitory activity and the protection of the stability of the enzyme. In Video S1, white carbons were used for the interacted residues, red carbons were used for the key amino acids, and violet carbons were used for highlighting the residues that formed halogen bonds with 7a.…”

“…Molecular dynamic simulations included calculations of radius of gyration (Rg), root-meansquare fluctuation (RMSF), and root-mean-square deviation (RMSD) via the Desmond application. [29,49,50] Furthermore, the in-silico docking procedure aimed to elucidate potential ligand interactions with acetylcholinesterase and β-secretase enzymes (PDBID: 4EY7 and 2ZJM, respectively). Docking studies were performed for compounds 6d, 7a, and 7e within the AChE active pocket and BACE-1 binding cavity.…”