Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues. Issue 48 (15th October 2015)

• Record Type: Journal Article
• Authors: Lesma, Giordano; Bassanini, Ivan; Bortolozzi, Roberta; Colletto, Chiara; Bai, Ruoli; Hamel, Ernest; Meneghetti, Fiorella; Rainoldi, Giulia; Stucchi, Mattia; Sacchetti, Alessandro; Silvani, Alessandra; Viola, Giampietro
• Is Part Of: Organic & biomolecular chemistry. Volume 13:Issue 48(2015)
• Page Start: 11633
• Page End: 11644
• Publication Date: 2015-10-15
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob01882j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A multicomponent strategy proved to be suitable for the concise and convergent generation of hemiasterlin derivatives, also including non-peptidic 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.