Syntheses and biological evaluation of M-COPA analogs derived from pentadienoic Weinreb amide.

IF 4.6 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-07-18 DOI:10.2183/pjab.101.029

Hisazumi Tsutsui, Daiki Usukura, Fumiya Watabe, Hiroki Okano, Ryo Hirata, Ryunosuke Shiogama, Yamato Kanai, Saki Kato, Yuki Asahara, Sayaka Chogi, Yingjia Lu, Haruka Hirai, Mai Kitamoto, Miho Kojima, Yuuki Obata, Motoyuki Shimonaka, Takatsugu Murata, Isamu Shiina

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引用次数: 0

Abstract

M-COPA (1), which contains diene and 3-picolylamine moieties in its side chain and seven stereogenic centers in a multisubstituted octalin skeleton, strongly inhibits the growth of several cancer cell lines. Expecting the improvement of conformational flexibility of basic and coordinating 3-pyridylmethylamino group on M-COPA and its physical properties, we efficiently synthesized its amine analogs by replacing its amide group with an amino group through the Weinreb amide-type Horner-Wadsworth-Emmons reaction. The cytotoxic properties of 1 and its analogs were evaluated against NCI-H226, a lung cancer cell line, HeLa, a cervical cancer cell line, and GIST-T1, a gastrointestinal stromal tumor cell line. The evaluation results indicated that the structural alteration from amide moiety to amine moiety lowered the pharmacological activity but remained strong cytotoxicity.

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五二烯Weinreb酰胺衍生M-COPA类似物的合成及生物学评价。

M-COPA(1)在其侧链中含有二烯和3-吡咯胺基团，在多取代的八聚体蛋白骨架中含有7个立体中心，能强烈抑制几种癌细胞系的生长。为了提高3-吡啶基甲基胺基在M-COPA上的构象灵活性及其物理性质，我们通过Weinreb酰胺型Horner-Wadsworth-Emmons反应将其酰胺基替换为氨基，从而高效地合成了其胺类类似物。研究了1及其类似物对肺癌细胞系NCI-H226、宫颈癌细胞系HeLa和胃肠道间质肿瘤细胞系GIST-T1的细胞毒性。评价结果表明，从酰胺段到胺段的结构改变降低了其药理活性，但仍具有较强的细胞毒性。

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来源期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 生物-综合性期刊

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The Proceedings of the Japan Academy Ser. B (PJA-B) is a scientific publication of the Japan Academy with a 90-year history, and covers all branches of natural sciences, except for mathematics, which is covered by the PJA-A. It is published ten times a year and is distributed widely throughout the world and can be read and obtained free of charge through the world wide web.