Abstract

Herein, the synthesis and biological evaluation of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole sulfonamide hybrids are discussed. All the synthesized molecules were assessed for anti-cancer and anti-TB activities using in vitro and in silico methods. The molecular docking study with CDK8 as a possible target for anti-cancer activity demonstrated that compounds 2, 3, 5, 7, 8, and 9 have a good binding affinity ranging from −8.7 to −10.3 kcal/mol against CDK8 (PDB 6T41) protein as compared with the standard drug 5-Fluorouracil (−5.0 kcal/mol). The in vitro anti-mycobacterial screening reveals that compounds 2 and 3 elicited moderate anti-TB activity with a MIC value of 25 µM. Compounds 2 and 3 exhibited moderate in vitro anti-proliferative potency against the cancer cell lines MCF-7 and HCT-116. Moreover, compound 3 exhibited a better anti-oxidant effect among all tested compounds. Some quantum chemical parameters and drug-likeness profiling of the molecules were modeled by density functional theory (DFT) and ADME studies. The obtained theoretical results are in good agreement with the experimental results.

摘要

在此，讨论了 6-氟-3-(哌啶-4-基)苯并[d]异恶唑磺酰胺杂化物的合成和生物学评价。使用体外和计算机方法评估所有合成分子的抗癌和抗结核活性。以 CDK8 作为抗癌活性的可能靶点的分子对接研究表明，化合物2、3、5、7、8和9对 CDK8 具有良好的结合亲和力，范围为 -8.7 至 -10.3 kcal/mol (PDB 6T41 ) 蛋白质与标准药物 5-氟尿嘧啶 (−5.0 kcal/mol) 相比。体外_抗分枝杆菌筛选表明，化合物2和3具有中等抗结核活性，MIC 值为 25 µM。化合物2和3对癌细胞系MCF-7和HCT-116表现出中等的体外抗增殖效力。此外，在所有测试的化合物中，化合物3表现出更好的抗氧化效果。通过密度泛函理论 (DFT) 和 ADME 研究对分子的一些量子化学参数和药物相似性分析进行了建模。所得理论结果与实验结果吻合良好。