Four 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.

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

Foschi, Francesca;Passarella, Daniele
2019-01-01

Abstract

Four 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.
2019
bivalent binders; microtubules; pironetin; thiocolchicine; tubulin binders; Chemistry (all)
Bonandi, Elisa; Foschi, Francesca; Marucci, Cristina; Dapiaggi, Federico; Sironi, Maurizio; Pieraccini, Stefano; Christodoulou, Michael S.; de Asís Ba...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2086295
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