A small family of structural analogues of the antimitotic tripeptides, hemiasterlins, have been designed and synthesized as potential inhibitors of tubulin polymerization. The effectiveness of a multicomponent approach was fully demonstrated by applying complementary versions of the isocyanide-based Ugi reaction. Compounds strictly related to the lead natural products, as well as more extensively modified analogues, have been synthesized in a concise and convergent manner. In some cases, biological evaluation provided evidence for strong cytotoxic activity (six human tumor cell lines) and for potent inhibition of tubulin polymerization.
Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues / G. Lesma, I. Bassanini, R. Bortolozzi, C. Colletto, R. Bai, E. Hamel, F. Meneghetti, G. Rainoldi, M. Stucchi, A. Sacchetti, A. Silvani, G. Viola. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 13:48(2015 Dec 28), pp. 11633-11644.
Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues
G. Lesma;I. Bassanini;F. Meneghetti;G. Rainoldi;M. Stucchi;A. Silvani;
2015
Abstract
A small family of structural analogues of the antimitotic tripeptides, hemiasterlins, have been designed and synthesized as potential inhibitors of tubulin polymerization. The effectiveness of a multicomponent approach was fully demonstrated by applying complementary versions of the isocyanide-based Ugi reaction. Compounds strictly related to the lead natural products, as well as more extensively modified analogues, have been synthesized in a concise and convergent manner. In some cases, biological evaluation provided evidence for strong cytotoxic activity (six human tumor cell lines) and for potent inhibition of tubulin polymerization.File | Dimensione | Formato | |
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