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双活性 1,4-二氢吡啶衍生物:设计、绿色合成及体外抗癌和抗氧化研究。

Dual active 1, 4-dihydropyridine derivatives: Design, green synthesis and in vitro anti-cancer and anti-oxidant studies.

机构信息

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.

出版信息

Bioorg Chem. 2020 Dec;105:104379. doi: 10.1016/j.bioorg.2020.104379. Epub 2020 Oct 15.

Abstract

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.

摘要

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。

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