A representative series of structural analogs of the antimitotic tripeptides hemiasterlins have been designed and synthesized, as potential inhibitors of tubulin polymerization. Relying also on a computational approach, we aimed to explore unknown extensive changes at the C-fragment, by incorporating the conformationally required double bond into five- and six-membered rings. Key steps of the synthetic strategy are a dynamic resolution affording theA-fragment in 97 % ee and the preparation of six new cyclic C fragments, all potentially able to interact with tubulin by means of H bonds. Unexpectedly, biological evaluation of these analogs did not provide evidences neither for cytotoxic effect nor for inhibition of tubulin polymerization.

Hemiasterlin analogues incorporating an aromatic, and heterocyclic type C-terminus: design, synthesis and biological evaluation / G. Lesma, A. Sacchetti, R. Bai, G. Basso, R. Bortolozzi, E. Hamel, A. Silvani, N. Vaiana, G. Viola. - In: MOLECULAR DIVERSITY. - ISSN 1381-1991. - 18:2(2014), pp. 357-373. [10.1007/s11030-014-9507-9]

Hemiasterlin analogues incorporating an aromatic, and heterocyclic type C-terminus: design, synthesis and biological evaluation

G. Lesma;A. Silvani;
2014

Abstract

A representative series of structural analogs of the antimitotic tripeptides hemiasterlins have been designed and synthesized, as potential inhibitors of tubulin polymerization. Relying also on a computational approach, we aimed to explore unknown extensive changes at the C-fragment, by incorporating the conformationally required double bond into five- and six-membered rings. Key steps of the synthetic strategy are a dynamic resolution affording theA-fragment in 97 % ee and the preparation of six new cyclic C fragments, all potentially able to interact with tubulin by means of H bonds. Unexpectedly, biological evaluation of these analogs did not provide evidences neither for cytotoxic effect nor for inhibition of tubulin polymerization.
Antimitotic peptides; Cytotoxicity; Dynamic resolution; Hemiasterlin; Tubulin
Settore CHIM/06 - Chimica Organica
MOLECULAR DIVERSITY
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/239095
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