Hemiasterlin analogues incorporating an aromatic,and heterocyclic type C-terminus: design,synthesis and biological evaluation |
| |
Authors: | Giordano Lesma Alessandro Sacchetti Rouli Bai Giuseppe Basso Roberta Bortolozzi Ernest Hamel Alessandra Silvani Nadia Vaiana Giampietro Viola |
| |
Institution: | 1. Dipartimento di Chimica, Università di Milano, via Golgi 19, Milan, 20133, Italy 2. Dipartimento di Chimica, Materiali ed Ing.Chimica ‘Giulio Natta’, Politecnico di Milano, p.zza Leonardo da Vinci 32, Milan, 20133, Italy 3. Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, MD, 21702, USA 4. Dipartimento di Salute della Donna e del Bambino, Università degli Studi di Padova, via Giustiniani 2, Padau, 35128, Italy
|
| |
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 the A-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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|