Synthesis of Thicolchicine-Based Conjugates: Investigation towards Bivalent Tubulin/Microtubules Binders

E. Bonandi, F. Foschi, C. Marucci, F. Dapiaggi, M. Sironi, S. Pieraccini, M.S. Christodoulou, F. de Asís Balaguer, J.F. Díaz, N. Zidar, D. Passarella

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimFour different hybrid compounds have been efficiently synthesized by conjugation of deacetylthiocolchicine with pironetin-inspired derivatives. The modest bioactivity and the apparent absence of interaction with α-tubulin is explained by a posteriori in silico investigation, which suggests a relevant distance between the thiocolchicine binding site and the proper pocket on the α-tubulin. The modest activity on resistant cells suggested that the lipophilic nature of the linker used renders the resulting compounds better substrates for p-Gp efflux pumps. The study better clarifies the design of bivalent compounds that target hetero tubulin/microtubules.
Original languageEnglish
Pages (from-to)98-102
JournalChemPlusChem
Volume84
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

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