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Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues.

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.

SUBMITTER: Lesma G

PROVIDER: S-EPMC4685954 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues.

Lesma Giordano G Bassanini Ivan I Bortolozzi Roberta R Colletto Chiara C Bai Ruoli R Hamel Ernest E Meneghetti Fiorella F Rainoldi Giulia G Stucchi Mattia M Sacchetti Alessandro A Silvani Alessandra A Viola Giampietro G

Organic & biomolecular chemistry 20151015 48

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, biologi ...[more]

PMID: 26467486

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