{"title":"Screening for antimicrobial and antioxidant activities of quinazolinone based isoxazole and isoxazoline derivatives, synthesis and In silico studies.","authors":"Nagaraju Myakala, Vishnu Thumma, Kotaiah Kandula, Nagamani Rayala, Lakshmi Satya Boddu, Kanaka Durga Bhavani Anagani","doi":"10.1007/s11030-024-11032-2","DOIUrl":null,"url":null,"abstract":"<p><p>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 IC<sub>50</sub> 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 IC<sub>50</sub> 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.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-11032-2","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
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.
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;