Synthesis, antiproliferative activity in cancer cells and theoretical studies of novel 6 alpha,7 beta-dihydroxyvouacapan-17 beta-oic acid Mannich base derivatives

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Natural products are great prototypes for the design of new anticancer agents. The plant-derived natural product 6 alpha,7 beta-dihydroxyvouacapan-17 beta-oic acid (1) is promising for the development of more potent antiproliferative agents against human cancer cells. Indeed, its lactone derivative 6 alpha-hydroxyvouacapan-7 beta,17 beta-lactone (2), a non-natural furanoditerpene, exhibited higher anticancer activity than compound 1. Herein, we describe the synthesis and antiproliferative activity of six new Mannich derivatives of compound 2 against nine cancer cell lines. Overall, our results revealed that Mannich derivatives 3-8 were more potent than compound 2 in inhibiting the proliferation of cancer cells. Theoretical studies also supported our findings, revealing the nucleophilic character of furan ring as an important feature for antiproliferative activity of the studied Mannich derivatives. (C) 2010 Elsevier Ltd. All rights reserved.182381728177Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq