National Centre for Sustainable Coastal Management, Anna University Campus, Chennai 600025, India.
Chemical Science Research Group, Division of Research and Development, Lovely Professional University, Phagwara, Punjab 144411. India; Dr. Param Laboratories, Phase-1, IDA, B.N. Reddy Nagar, Cherlapally, Hyderabad, Telangana 500062, India.
Bioorg Chem. 2020 Dec;105:104379. doi: 10.1016/j.bioorg.2020.104379. Epub 2020 Oct 15.
The present work describes the design of 1,4-dihydropyridines (1,4-DHPs) with diverse variations in structural and functional groups. The physico-chemical properties and drug-like molecule nature evaluations were carried out using SWISSADME. A simple, economical, eco-friendly, water-mediated and Para-Toluene sulfonic acid catalysed multicomponent and one-pot synthetic method from nitroketene N, S- acetals (NMSM) and corresponding aldehydes has been developed. All compounds (6a-u and 13a-h) were subjected to in vitro assays against two important human cancer cell lines Viz. are Laryngeal carcinoma (Hep2) and Lung adenocarcinoma (A549) cells. The reduction level of DPPH (%) used to evaluate the anti-oxidant properties. The 1,4-DHP derivatives, 6o, 6u and 6l displayed the potent anti-cancer activity with IC value of 10 µM, 14 µM and 10 µM against the Hep2 and 8 µM, 9 µM and 50 µM against the A549 cells. Similarly, the anti-oxidant properties of 6o, 6l and 6u at a standard concentration of 50 µg, are found to be 70.12%, 63.90% and 59.57% respectively favours the 1,4-DHP derivatives dual activity potentials. The compounds, 6o and 6l found to be equivalent with standard drug, Doxorubicin.
本工作描述了具有不同结构和功能基团变化的 1,4-二氢吡啶(1,4-DHPs)的设计。使用 SWISSADME 进行了物理化学性质和类似药物分子性质的评估。已经开发出了一种从硝基烯 N, S-缩醛(NMSM)和相应的醛出发,采用简单、经济、环保、水介导和对甲苯磺酸催化的多组分一锅合成方法。所有化合物(6a-u 和 13a-h)都进行了体外测试,针对两种重要的人类癌细胞系,即喉癌(Hep2)和肺腺癌(A549)细胞。使用 DPPH(%)还原水平来评估抗氧化性能。1,4-DHP 衍生物 6o、6u 和 6l 表现出较强的抗癌活性,对 Hep2 的 IC 值为 10µM、14µM 和 10µM,对 A549 的 IC 值为 8µM、9µM 和 50µM。同样,在标准浓度为 50µg 时,6o、6l 和 6u 的抗氧化性能分别为 70.12%、63.90%和 59.57%,这有利于 1,4-DHP 衍生物的双重活性潜力。化合物 6o 和 6l 被发现与标准药物阿霉素等效。