新型磺胺类吡唑棒状吡唑啉衍生物的合成、生物学评价及分子对接研究。

IF 4.3 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
ACS Omega Pub Date : 2025-02-11 eCollection Date: 2025-02-25 DOI:10.1021/acsomega.4c10198
Mayursinh Zala, Jwalant J Vora, Vijay M Khedkar, Atiah H Almalki, Sunil Tivari, Rupal Jatvada
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引用次数: 0

摘要

为了克服耐多药结核病(MDR-TB)问题,我们报道了在催化量Conc存在下,以1-(7-氯喹啉-4-基)-3-(噻吩/呋喃-2-基)- 1h -吡唑-4-醛查尔酮衍生物(8a-p)和4-肼基苯磺酰胺(2)为原料,合成了新型磺胺基吡唑-棒状吡唑啉衍生物(9a-p)。盐酸和乙醇作为溶剂。新合成的化合物对结核分枝杆菌H37Rv菌株进行了抑菌试验,其中化合物9g、9h、9i、9j、9m和9n的抑菌效果最好。采用ESI-MS、FT-IR、NMR和UV等不同的光谱技术对新合成的类似物进行了结构表征。此外,对分枝杆菌InhA活性位点的分子对接研究结果表明,这些化合物的结合强度在-9.714至-8.647之间。化合物4-(1'-(7-氯喹啉-4-基)-5-(4-氟苯基)-3'-(噻吩-2-基)-3,4-二氢-1' h,2H-[3,4'-联吡唑]-2-基)苯磺酰胺(9g)对结核分枝杆菌H37Rv具有良好的抗结核活性,MIC为10.2 μg/mL,抑制率为99%,对接评分为-9.714,滑翔能量为-64.183 kcal/mol。计算机ADMET预测表明合成的新分子与药物相似。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development of Novel Sulfonamide-Based Pyrazole-Clubbed Pyrazoline Derivatives: Synthesis, Biological Evaluation, and Molecular Docking Study.

To overcome the multidrug-resistant tuberculosis (MDR-TB) problem, we reported the synthesis of novel sulfonamide-based pyrazole-clubbed pyrazoline derivatives (9a-p) by reaction of 1-(7-chloroquinolin-4-yl)-3-(thiophene/furan-2-yl)-1H-pyrazole-4-carbaldehyde chalcone derivatives (8a-p) and 4-hydrazinylbenzenesulfonamide (2) in the presence of a catalytic amount of Conc. HCl and ethanol are used as a solvent. Newly synthesized compounds were tested against the Mycobacterium tuberculosis H37Rv strain, wherein compounds 9g, 9h, 9i, 9j, 9m, and 9n were found to be the most potent. The structures of the newly synthesized analogues were determined by different spectroscopic techniques like ESI-MS, FT-IR, NMR, and UV methods. Additionally, molecular docking studies of the active site of mycobacterial InhA resulted in well-aggregated elucidations for these compounds with a binding strength in the range of -9.714 to -8.647. Compound 4-(1'-(7-chloroquinolin-4-yl)-5-(4-fluorophenyl)-3'-(thiophen-2-yl)-3,4-dihydro-1'H,2H-[3,4'-bipyrazol]-2-yl)benzenesulfonamide (9g) shows excellent antitubercular activity against M. tuberculosis H37Rv, achieving an MIC of 10.2 μg/mL and 99% inhibition with a docking score of -9.714 and a Glide energy of -64.183 kcal/mol. In silico ADMET predictions indicated the drug-likeness of synthesized novel molecules.

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来源期刊
ACS Omega
ACS Omega Chemical Engineering-General Chemical Engineering
CiteScore
6.60
自引率
4.90%
发文量
3945
审稿时长
2.4 months
期刊介绍: ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.
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