title: 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.
authors.affiliation: Università di Milano, Dipartimento di Chimica, via Golgi 19, Milano, 20133, Italy. alessandra.silvani@unimi.it.
authors.forename: Giordano
authors.initials: G
authors.lastname: Lesma
authors.forename: Ivan
authors.initials: I
authors.lastname: Bassanini
authors.forename: Roberta
authors.initials: R
authors.lastname: Bortolozzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Colletto
authors.forename: Ruoli
authors.initials: R
authors.lastname: Bai
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Fiorella
authors.initials: F
authors.lastname: Meneghetti
authors.forename: Giulia
authors.initials: G
authors.lastname: Rainoldi
authors.forename: Mattia
authors.initials: M
authors.lastname: Stucchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sacchetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Silvani
authors.forename: Giampietro
authors.initials: G
authors.lastname: Viola
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry; D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000447:Aldehydes; D050256:Antimitotic Agents; D009570:Nitriles; D009842:Oligopeptides; C467070:hemiasterlin