Department of Chemistry, National Institute of Technology, Hamirpur, Himachal Pradesh, India.
J Biomol Struct Dyn. 2022 Sep;40(15):7052-7069. doi: 10.1080/07391102.2021.1893818. Epub 2021 Mar 11.
Isoleucine substituted analogues with secondary sulfonamide group (I-I) have been synthesized. Structures of synthesized analogues have been confirmed by Fourier Transform-Infrared Red, Nuclear Magnetic Resonance (H and C) and ESI-MS spectroscopic tools. Cytotoxic screenings of synthesized analogues have been done on MCF-7 (breast), Prostate Cancer-3 (PC-3) and A549 (lung) cancer cell lines. -(1-isobutyl-2-oxo-2-anilinoethyl) -toluene sulfonamide (I) screened to be better cytotoxic agent on MCF-7 and A549 cell lines whereas -(1-isobutyl-2-oxo-2--chloroanilino ethyl) benzene sulfonamide (I) against PC-3 cell line. Cell cycle analysis of -(1-isobutyl-2-oxo-2-anilinoethyl) -toluene sulfonamide (I) analogue has been carried out on A549 cell line in comparison to control and Vinblastine (standard drug). Complete arrest in G0 and G1 phase along with mild disturbance in S-phase of cell cycle has been observed. The screened analogues (I-I) also showed good antifungal and antibacterial potential against gram positive as well as gram negative strains. Computer simulation indicated good bioactivity prediction by the 'Lipinski rule' and synthesized analogues did not violate this rule. Docking study of isoleucine sulfonamide analogues (I-I) were carried out to determine the possible interaction sites of the analogues with p53 tumor suppressor-DNA complex and demonstrate that the analogues confirmed binding and inhibition with the most mutated residues of p53. Density functional theory has been used to correlate the electronic and chemical properties of analogues and they were found to be stable and chemically reactive. Thus the results suggest that isoleucine substituted sulfonamide analogues can serve as a structural model for the design of anticancer agents, antibacterial agents as well as antifungal agents with better inhibitory potential.Communicated by Ramaswamy H. Sarma.
已合成了具有二级磺酰胺基的异亮氨酸取代类似物（I-I）。通过傅里叶变换红外、核磁共振（H 和 C）和 ESI-MS 光谱工具确认了合成类似物的结构。对 MCF-7（乳腺）、前列腺癌-3（PC-3）和 A549（肺）癌细胞系进行了合成类似物的细胞毒性筛选。-（1-异丁基-2-氧代-2-苯胺基乙基）-甲苯磺酰胺（I）对 MCF-7 和 A549 细胞系显示出更好的细胞毒性，而-（1-异丁基-2-氧代-2--氯苯胺基乙基）苯磺酰胺（I）对 PC-3 细胞系具有活性。与对照和长春碱（标准药物）相比，已对 A549 细胞系进行了-（1-异丁基-2-氧代-2-苯胺基乙基）-甲苯磺酰胺（I）类似物的细胞周期分析。观察到细胞周期的 G0 和 G1 期完全停滞，同时 S 期受到轻微干扰。筛选出的类似物（I-I）也对革兰氏阳性和革兰氏阴性菌株表现出良好的抗真菌和抗菌潜力。计算机模拟表明，“利宾斯基规则”可以很好地预测生物活性，而合成的类似物没有违反该规则。对异亮氨酸磺酰胺类似物（I-I）进行了对接研究，以确定类似物与 p53 肿瘤抑制-DNA 复合物的可能相互作用位点，并证明类似物与 p53 中最突变的残基确认结合和抑制。密度泛函理论被用于关联类似物的电子和化学性质，发现它们是稳定的和有反应性的。因此，结果表明，异亮氨酸取代的磺酰胺类似物可以作为设计抗癌、抗菌和抗真菌药物的结构模型，具有更好的抑制潜力。由 Ramaswamy H. Sarma 传达。
