Design, synthesis, and biological evaluation of biotinylated colchicine derivatives as potential antitumor agents

Abstract

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.

Keywords:

• Colchicine
• adverse effects
• conjugate
• biotin
• disulphide bond

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (10.1080/14756366.2022.2024999)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We gratefully acknowledge the National Natural Science Foundation of China [81673293 and 81602969]. This work was also supported by the Program for Innovative Research Team of the Ministry of Education.