海石酰胺及其类似物的设计、合成与抗肿瘤生物学评价

Design, Synthesis, and Antitumor Biological Evaluation of Galaxamide and Its Analogs.

作者信息

Guo Yanyan, Fan Huixia, Luo Zhiqiang, Yang Jian, Liu Guodu

机构信息

Inner Mongolia Key Laboratory of Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Inner Mongolia University (South Campus), 24 Zhaojun Road, Hohhot 010030, China.

State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

出版信息

Molecules. 2025 May 29;30(11):2362. doi: 10.3390/molecules30112362.

DOI:10.3390/molecules30112362

PMID:40509249

Abstract

Galaxamide, an -methylated cyclo-pentapeptide containing five -leucines isolated from , has shown significant antitumor activity. This unique cyclo-pentapeptide offered a fresh skeleton for structural modifications. Herein, galaxamide and its 23 analogs (~) were designed and synthesized by substituting -leucine with various proteinogenic amino acids or altering the amino acid configuration using the "3 + 2" strategy, and the in vitro antitumor activity of these cyclopeptides was studied utilizing the CCK-8 assay against two human tumor cell lines (A549 and K562) and one human normal cell line (293T). The total yields of galaxamide and its analogs reached 9.7% and 9.1-16.0%, respectively. CCK-8 assays demonstrated that these compounds showed broad-spectrum antitumor activity, with exhibiting outstanding activity against K562 cells (IC = 4.2 µM). The anticancer efficacy of galaxamide analogs against tumor cell lines was significantly influenced by the quantity of D-leucines and the -leucine position.

摘要

加拉沙胺是一种从[具体来源未提及]中分离得到的含五个亮氨酸的α-甲基化环五肽，已显示出显著的抗肿瘤活性。这种独特的环五肽为结构修饰提供了一个全新的骨架。在此，通过使用“3 + 2”策略用各种蛋白质氨基酸取代亮氨酸或改变氨基酸构型，设计并合成了加拉沙胺及其23种类似物（~），并利用CCK - 8测定法研究了这些环肽对两种人类肿瘤细胞系（A549和K562）和一种人类正常细胞系（293T）的体外抗肿瘤活性。加拉沙胺及其类似物的总产率分别达到9.7%和9.1 - 16.0%。CCK - 8测定表明这些化合物具有广谱抗肿瘤活性，其中[具体化合物未提及]对K562细胞表现出出色的活性（IC = 4.2 µM）。加拉沙胺类似物对肿瘤细胞系的抗癌疗效受到D - 亮氨酸数量和亮氨酸位置的显著影响。