Mayursinh Zala, Jwalant J Vora, Vijay M Khedkar, Atiah H Almalki, Sunil Tivari, Rupal Jatvada
{"title":"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。","authors":"Mayursinh Zala, Jwalant J Vora, Vijay M Khedkar, Atiah H Almalki, Sunil Tivari, Rupal Jatvada","doi":"10.1021/acsomega.4c10198","DOIUrl":null,"url":null,"abstract":"<p><p>To overcome the multidrug-resistant tuberculosis (MDR-TB) problem, we reported the synthesis of novel sulfonamide-based pyrazole-clubbed pyrazoline derivatives <b>(9a-p)</b> by reaction of 1-(7-chloroquinolin-4-yl)-3-(thiophene/furan-2-yl)-1<i>H</i>-pyrazole-4-carbaldehyde chalcone derivatives <b>(8a-p)</b> and 4-hydrazinylbenzenesulfonamide <b>(2)</b> in the presence of a catalytic amount of Conc. HCl and ethanol are used as a solvent. Newly synthesized compounds were tested against the <i>Mycobacterium tuberculosis</i> H<sub>37</sub>Rv strain, wherein compounds <b>9g</b>, <b>9h</b>, <b>9i</b>, <b>9j</b>, <b>9m</b>, and <b>9n</b> 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 <b>-9.714</b> to <b>-8.647</b>. Compound 4-(1'-(7-chloroquinolin-4-yl)-5-(4-fluorophenyl)-3'-(thiophen-2-yl)-3,4-dihydro-1<i>'H</i>,2<i>H</i>-[3,4'-bipyrazol]-2-yl)benzenesulfonamide <b>(9g)</b> shows excellent antitubercular activity against M. tuberculosis H<sub>37</sub>Rv, achieving an MIC of <b>10.2 μg/mL</b> and <b>99%</b> inhibition with a docking score of <b>-9.714</b> and a Glide energy of <b>-64.183 kcal/mol</b>. In silico ADMET predictions indicated the drug-likeness of synthesized novel molecules.</p>","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"10 7","pages":"7120-7130"},"PeriodicalIF":4.3000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866009/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development of Novel Sulfonamide-Based Pyrazole-Clubbed Pyrazoline Derivatives: Synthesis, Biological Evaluation, and Molecular Docking Study.\",\"authors\":\"Mayursinh Zala, Jwalant J Vora, Vijay M Khedkar, Atiah H Almalki, Sunil Tivari, Rupal Jatvada\",\"doi\":\"10.1021/acsomega.4c10198\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>To overcome the multidrug-resistant tuberculosis (MDR-TB) problem, we reported the synthesis of novel sulfonamide-based pyrazole-clubbed pyrazoline derivatives <b>(9a-p)</b> by reaction of 1-(7-chloroquinolin-4-yl)-3-(thiophene/furan-2-yl)-1<i>H</i>-pyrazole-4-carbaldehyde chalcone derivatives <b>(8a-p)</b> and 4-hydrazinylbenzenesulfonamide <b>(2)</b> in the presence of a catalytic amount of Conc. 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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.
ACS OmegaChemical 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.