Design, synthesis, and biological evaluation of biotinylated colchicine derivatives as potential antitumor agents
| Autor: | Chao Wang, Yujing Zhang, Zeyu Wang, Yuelin Li, Qi Guan, Dongming Xing, Weige Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 37, Iss 1, Pp 417-426 (2022) |
| Druh dokumentu: | article |
| ISSN: | 1475-6366 1475-6374 14756366 |
| DOI: | 10.1080/14756366.2021.2013832 |
| Popis: | Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovering new anti-tumour drugs to improve tumour targeting effects and reduce off-target toxicities. Colchicine is one of the most prominent and historically microtubule-targeting drugs, but its clinical applications are hindered by notorious adverse effects. In this study, we presented a novel tumour-specific conjugate 9 that consists of deacetylcolchicine (Deac), biotin, and a cleavable disulphide linker. 9 was found to exhibit potent anti-tumour activity and exerted higher selectivity between tumour and nontarget cells than Deac. The targeting moiety biotin might enhance the transport capability and selectivity of 9 to tumour cells via biotin receptor-mediated endocytosis. The tubulin polymerisation activity of 9 (with DTT) was close to the parent drug Deac. These preliminary results suggested that 9 is a high potency and reduced toxicity antitumor agent and worthy of further investigation. |
| Databáze: | Directory of Open Access Journals |
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