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

被引:15
作者
Evren, Asaf Evrim [2 ,4 ]
Karaduman, Abdullah Burak [1 ]
Saglik, Begum Nurpelin [2 ,3 ]
Ozkay, Yusuf [2 ,3 ]
Yurttas, Leyla [2 ]
机构
[1] Anadolu Univ, Fac Pharm, Dept Pharmaceut Toxicol, TR-26470 Eskisehir, Turkiye
[2] Anadolu Univ, Fac Pharm, Dept Pharmaceut Chem, TR-26470 Eskisehir, Turkiye
[3] Anadolu Univ, Fac Pharm, Cent Res Lab, TR-26470 Eskisehir, Turkiye
[4] Bilecik Seyh Edebali Univ, Vocat Sch Hlth Serv, Dept Pharm Serv, TR-11000 Bilecik, Turkiye
来源
ACS OMEGA | 2023年 / 8卷 / 01期
关键词
ANTIFUNGAL AGENTS; MOLECULAR-BASIS; HUMAN CYP19; INHIBITION; AROMATASE; RESISTANCE; INSIGHTS; 14-ALPHA-DEMETHYLASE; ANTIBACTERIAL; CHALLENGES;
D O I
10.1021/acsomega.2c06871
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 14a-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 structureactivity 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.
引用
收藏
页码:1410 / 1429
页数:20
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