Synthesis and evaluation of di-heterocyclic benzazole compounds as potential antibacterial and anti-biofilm agents against Staphylococcus aureus

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mine Buga Aktekin, Zehra Oksuz, Burcin Turkmenoglu, Erman Salih Istifli, Mehmet Kuzucu, Oztekin Algul
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Abstract

Cumulative escalation in antibiotic-resistant pathogens necessitates the quest for novel antimicrobial agents, as current options continue to diminish bacterial resistance. Herein, we report the synthesis of di-heterocyclic benzazole structures (12–19) and their in vitro evaluation for some biological activities. Compounds 16 and 17 demonstrated potent antibacterial activity (MIC = 7.81 μg/mL) against Staphylococcus aureus, along with significant anti-biofilm activity. Noteworthy is the capability of Compound 17 to inhibit biofilm formation by at least 50% at sub-MIC (3.90 μg/mL) concentration. Furthermore, both compounds exhibited the potential to inhibit preformed biofilm by at least 50% at the MIC concentration (7.81 μg/mL). Additionally, Compounds 16 and 17 were examined for cytotoxic effects in HFF-1 cells, using the MTT method, and screened for binding interactions within the active site of S. aureus DNA gyrase using in silico molecular docking technique, employing AutoDock 4.2.6 and Schrödinger Glidse programs. Overall, our findings highlight Compounds 16 and 17 as promising scaffolds warranting further optimization for the development of effective antibacterial and anti-biofilm agents.

Abstract Image

合成和评估二环苯并唑化合物作为抗金黄色葡萄球菌的潜在抗菌剂和抗生物膜剂。
抗生素耐药性病原体的不断增加,使得人们有必要寻找新型抗菌剂,因为目前的选择仍在不断减少细菌的耐药性。在此,我们报告了二环苯并唑结构(12-19)的合成及其体外生物活性评估。化合物 16 和 17 对金黄色葡萄球菌具有强效抗菌活性(MIC = 7.81 μg/mL),同时还具有显著的抗生物膜活性。值得注意的是,化合物 17 在亚 MIC(3.90 μg/mL)浓度下能抑制生物膜形成至少 50%。此外,这两种化合物在 MIC 浓度(7.81 μg/mL)下都能抑制已形成的生物膜至少 50%。此外,利用 MTT 法检测了化合物 16 和 17 对 HFF-1 细胞的细胞毒性作用,并采用 AutoDock 4.2.6 和 Schrödinger Glidse 程序,利用硅学分子对接技术筛选了金黄色葡萄球菌 DNA 回旋酶活性位点内的结合相互作用。总之,我们的研究结果表明,化合物 16 和 17 是很有前途的支架,值得进一步优化,以开发有效的抗菌剂和抗生物膜剂。
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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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