Design, Synthesis, and Biological Evaluation of quinoxaline bearing tetrahydropyridine derivatives as anticancer, antioxidant, and anti-tubercular agents.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Current computer-aided drug design Pub Date : 2022-08-04 DOI:10.2174/1573409918666220804142753

Ganesh Pavale, Poornima Acharya, Nilesh Korgavkar, M M V Ramana

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引用次数: 0

Abstract

Background: Quinoxaline and Tetrahydropyridine derivatives showed various biological properties. The combination of these two scaffolds may contribute to good biological activity and may give novel and efficacious bioactive candidates.

Objective: The present study aimed to identify bioactive agents with quinoxaline bearing tetrahydropyridine derivatives possessing anticancer, antioxidant, and anti-tubercular agents.

Method: A series of novel quinoxaline bearing tetrahydropyridine derivatives have been designed and synthesized in good yields. The synthetic protocol involves three-component Povarov reactions of 6-amino quinoxaline, propenyl guaethol, and substituted aldehydes using BF3•OEt2 as catalyst. The newly synthesized molecules were evaluated for their anticancer activity against four cell lines, i.e. A-549, MCF-7, PC-3, and HepG2.

Results: The results from in vitro assay indicated that compound 4a proved to be as potent as the standard drug adriamycin against all cell lines with GI50 values <10 μg/ml. Compounds 4b, 4f, and 4i exhibited good cytotoxicity against A-549 cell line. All synthesized molecules were evaluated for their antioxidant activity and the results revealed that the compounds 4a, 4b, and 4i showed promising antioxidant activities against DPPH and H2O2 scavenging. In addition, the anti-mycobacterial activity of the synthesized compounds against MTB H37Rv strain was determined using MABA method. The results indicate that the compounds 4a, 4b, 4g, and 4i showed better anti-mycobacterial activity than the standard drugs pyrazinamide, ciprofloxacin and streptomycin with MIC value 1.6 μg/ml. Furthermore, molecular docking studies and ADME properties showed good pharmacokinetic profile and drug-likeness properties.

Conclusion: These studies showed that a series of novel quinoxaline bearing tetrahydropyridine derivatives exhibit anticancer, anti-mycobacterial, and antioxidant activities.

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喹喔啉类四氢吡啶衍生物作为抗癌、抗氧化和抗结核药物的设计、合成和生物学评价。

背景：喹喔啉和四氢吡啶衍生物具有多种生物特性。这两种支架的结合可能有助于产生良好的生物活性，并可能产生新颖、有效的生物活性候选物：本研究旨在确定具有抗癌、抗氧化和抗结核作用的喹喔啉-四氢吡啶衍生物的生物活性物质：方法：设计并合成了一系列新型喹喔啉类四氢吡啶衍生物，产量良好。合成方案包括以 BF3-OEt2 为催化剂，对 6-氨基喹喔啉、丙烯基愈创木酚和取代醛进行三组分 Povarov 反应。评估了新合成分子对四种细胞系（即 A-549、MCF-7、PC-3 和 HepG2）的抗癌活性：体外检测结果表明，化合物 4a 对所有细胞株的 GI50 值与标准药物阿霉素相同：这些研究表明，一系列新型喹喔啉类四氢吡啶衍生物具有抗癌、抗霉菌和抗氧化活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current computer-aided drug design 医学-计算机：跨学科应用

CiteScore

3.70

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.