Screening for antimicrobial and antioxidant activities of quinazolinone based isoxazole and isoxazoline derivatives, synthesis and In silico studies.

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED
Nagaraju Myakala, Vishnu Thumma, Kotaiah Kandula, Nagamani Rayala, Lakshmi Satya Boddu, Kanaka Durga Bhavani Anagani
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Abstract

Two novel series of quinazolinone based isoxazole and isoxazoline hybrid compounds were synthesized from 6-aminoquinazolinone as a key precursor. The title compounds were achieved in synthetic routes via propargylation and allylation reactions of the precursor followed by cyclization with various chloroximes. The new compounds 4a-g and 6a-g were screened for their antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria and two fungi by employing Ampicillin and Itraconazole as standard reference. Among all, the 4-bromosubstituted analogues in isoxazole series 4d and in isoxazoline series 6d demonstrated potent activity against all bacterial and fungal strains compared to Ampicillin as well as Itraconazole. The MIC of these compounds were determined as 0.012 μM. The antioxidant investigation revealed that compounds 4f and 6f with dimethyl substitution, exhibited significant activity. Their respective IC50 values were 1.28 ± 0.33, 1.39 ± 0.38 µM and 1.07 ± 0.24, 1.10 ± 0.26 µM, when compared to Ascorbic acid. The compounds 4 g and 6 g with dichloro substitution, exhibited promising results with IC50 values were 2.72 ± 0.34 µM and 2.78 ± 0.41 µM for 4 g, and 2.24 ± 0.93 µM and 2.45 ± 0.53 µM for 6 g, respectively. Their antimicrobial and antioxidant activities were authenticated by the molecular docking study against crystal structure of DNA gyrase and NADPH oxidase. The predicted ADME properties of these molecules progressed favourable drug-likeness properties.

基于喹唑啉酮的异噁唑和异噁唑啉衍生物的抗菌和抗氧化活性筛选、合成和硅学研究。
以 6-氨基喹唑啉酮为关键前体,合成了两个新系列的喹唑啉酮基异噁唑和异噁唑啉杂化物。标题化合物的合成路线是先将前体进行丙炔化和烯丙炔化反应,然后与各种氯肟进行环化反应。以氨苄西林和伊曲康唑为标准参照物,筛选了新化合物 4a-g 和 6a-g 对两种革兰氏阳性菌、两种革兰氏阴性菌和两种真菌的抗菌活性。与氨苄西林和伊曲康唑相比,异噁唑系列 4d 和异噁唑啉系列 6d 中的 4-溴取代类似物对所有细菌和真菌菌株都有很强的活性。这些化合物的 MIC 值为 0.012 μM。抗氧化研究表明,以二甲基取代的化合物 4f 和 6f 具有显著的活性。与抗坏血酸相比,它们的 IC50 值分别为 1.28 ± 0.33、1.39 ± 0.38 µM 和 1.07 ± 0.24、1.10 ± 0.26 µM。以二氯取代的化合物 4 g 和 6 g 表现出良好的效果,其 IC50 值分别为:4 g 2.72 ± 0.34 µM 和 2.78 ± 0.41 µM,6 g 2.24 ± 0.93 µM 和 2.45 ± 0.53 µM。根据 DNA 回旋酶和 NADPH 氧化酶的晶体结构进行的分子对接研究证实了它们的抗菌和抗氧化活性。根据预测,这些分子的 ADME 特性具有良好的药物相似性。
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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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