以腙和吡唑支架为靶向DNA Gyraze酶的新型喹唑啉-4(3H)酮衍生物

IF 2.3 Q3 PHARMACOLOGY & PHARMACY
Eman M. Mohi El-Deen, E. Nossier, Eman A. Karam
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引用次数: 8

摘要

本工作包括合成一系列新的喹唑啉-4(3H)-酮化合物(4a–f,5a–d)作为抗菌剂。合成了起始化合物2-肼基喹唑啉-4(3H)-酮(2),并用不同的羰基化合物处理,得到腙衍生物4a–f。此外,用DMF/POCl3混合物处理腙衍生物4a–d,得到甲酰基吡唑衍生物5a–d。所有目标化合物都被评估为抗四种细菌和四种真菌菌株的抗菌剂。与参考抗生素相比,大多数测试化合物显示出强大的抗菌活性。5a显示出最有效的抗菌活性,MIC值在(1-16)μg/mL范围内。此外,评估了对大肠杆菌最有效的化合物对大肠杆菌DNA旋转酶的抑制活性,而目标化合物4a、5a、5c和5d对目标酶显示出最有效的抑制作用,IC50值范围为3.19至4.17µM。此外,对针对靶大肠杆菌DNA旋转酶的最具活性的化合物进行了分子对接研究,以确定它们在酶活性位点内的结合亲和力。此外,这些化合物的ADME评估预测了它们的高口服生物利用度和良好的胃肠道吸收。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
New Quinazolin-4(3H)-one Derivatives Incorporating Hydrazone and Pyrazole Scaffolds as Antimicrobial Agents Targeting DNA Gyraze Enzyme
The present work includes the synthesis of a new series of quinazolin-4(3H)-one compounds (4a–f, 5a–d) as antimicrobial agents. The starting compound, 2-hydrazinylquinazolin-4(3H)-one (2), was synthesized and treated with different carbonyl compounds to afford the hydrazone derivatives 4a–f. In addition, the hydrazone derivatives 4a–d were treated with a DMF/POCl3 mixture to give the formyl-pyrazole derivatives 5a–d. All the target compounds were evaluated as antimicrobial agents against four bacterial and four fungal strains. The majority of the tested compounds showed potent antimicrobial activity compared with the reference antibiotics. The most potent antimicrobial activity was shown by 5a with MIC values in the range (1–16) μg/mL. In addition, the most potent compounds against E. coli were evaluated for their inhibitory activity against E. coli DNA gyrase, whereas the target compounds 4a, 5a, 5c, and 5d showed the most potent inhibition to the target enzyme with IC50 values ranging from 3.19 to 4.17 µM. Furthermore, molecular docking studies were performed for the most active compounds against the target E. coli DNA gyrase to determine their binding affinity within the enzyme’s active site. Moreover, ADME evaluations of these compounds predicted their high oral bioavailability and good GI absorption.
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来源期刊
Scientia Pharmaceutica
Scientia Pharmaceutica Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.60
自引率
4.00%
发文量
67
审稿时长
10 weeks
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