Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore |
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Authors: | Ming-Jiang Wu Dong-Mei Wu Jing-Bo Chen Jing-Feng Zhao Liang Gong Ya-Xiao Gong Yan Li Xiao-Dong Yang Hongbin Zhang |
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Institution: | 1. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China;2. State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, PR China |
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Abstract: | Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,β-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC50 values of 0.25–1.72?µM. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and apoptosis in SMMC-7721 cell lines. |
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Keywords: | Allogibberic acid 1 2 3-Triazole Cytotoxic activity Cell cycle Apoptosis |
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