Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling,Molecular Diversity

当前位置： X-MOL 学术 › Mol. Divers. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling
Molecular Diversity ( IF 3.9 ) Pub Date : 2021-08-02 , DOI: 10.1007/s11030-021-10287-3
Tejeswara Rao Allaka ₁ , Bhaskar Kummari ₁ , Naveen Polkam ₁ , Naveen Kuntala ₁ , Kalyani Chepuri ₂ , Jaya Shree Anireddy ₁

Affiliation

Design and synthesis of novel series of 1,3,4-oxadiazoles containing FQs derivatives and screened their antibacterial, antimycobacterial properties. The synthesized compounds were characterized by different spectral techniques like IR, ¹H NMR, ¹³C NMR, mass and elemental analysis. The results of the antimicrobial activity and compounds 6d, 6b, 6e, 6f and 6a demonstrated potent antibacterial activities with zone of inhibition of 42, 36, 37, 34 and 30 mm against S. aureus, E. faecalis, S. pneumoniae, E. coli and K. pneumoniae, respectively. 1,3,4-Oxadiazole derivatives 6a, 6b, 6 g were showed excellent antimycobacterial activity against M. smegmatis H₃₇Rv with MICs 22.35, 16.20, 20.28 µg/mL, respectively. FQs 6d and 6b exhibited highest hydrogen bonding interactions with Asp83 (3.11 A˚), Ser80 (2.15 A˚) Asp27 (σ-σ), Arg87 (Π-Π), Arg87 (Π-Π), Ser80 (σ-σ), Ala84 (σ-σ) and binding energies ΔG = − 6.41, − 6.97 kcal/mol with active site of topoisomerase-IV from S. pneumoniae [4KPE]. We performed a computational investigation of compounds 6a–j for their absorption, distribution, metabolism and excretion (ADME) properties by using the Molinspiration, Molsoft toolkits. The ligands 6f, 6d and 6b reveal the highest pharmacokinetic properties and possess maximum drug-likeness model score 1.59, 1.46 and 1.23, respectively.

Graphic abstract

中文翻译：

氟喹诺酮类的新型杂环 1,3,4-恶二唑衍生物作为强效抗菌剂：合成和计算分子模型

设计和合成新系列的含 FQs 衍生物的 1,3,4-恶二唑，并筛选其抗菌、抗分枝杆菌特性。合成的化合物通过IR、¹ H NMR、¹³ C NMR、质量和元素分析等不同的光谱技术进行表征。抗菌活性的结果和化合物6d、6b、6e、6f和6a证明了对金黄色葡萄球菌、粪肠球菌、肺炎链球菌、大肠杆菌的有效抗菌活性，抑制区为 42、36、37、34 和 30 mm . 大肠杆菌和K. 肺炎, 分别. 1,3,4-恶二唑衍生物6a、6b、6g对耻垢分枝杆菌 H ₃₇ Rv表现出优异的抗分枝杆菌活性，MIC 分别为 22.35、16.20、20.28 µg/mL。FQ 6d和6b与 Asp83 (3.11 A˚)、Ser80 (2.15 A˚) Asp27 (σ-σ)、Arg87 (Π-Π)、Arg87 (Π-Π)、Ser80 (σ-σ) 表现出最高的氢键相互作用, Ala84 (σ-σ) 和结合能 ΔG = - 6.41, - 6.97 kcal/mol，具有来自肺炎链球菌的拓扑异构酶-IV 的活性位点[4KPE]。我们使用 Molinspiration、Molsoft 工具包对化合物6a-j的吸收、分布、代谢和排泄 (ADME) 特性进行了计算研究。配体6f、6d和6b揭示了最高的药代动力学特性，并具有最大的药物相似性模型得分分别为 1.59、1.46 和 1.23。

图形摘要

更新日期：2021-08-02

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11