Effect of 6 alpha,7 beta-dihydroxyvouacapan-17 beta-oic acid and its lactone derivatives on the growth of human cancer cells

Abstract

The furanditerpene 6 alpha,7 beta-dihydroxyvouacapan-17 beta-oic acid (1) is a natural product biosynthesized by some species from the genus Pterodon (Leguminosae). This secondary metabolite has multiple biological activities that include anti-inflammatory, analgesic, plant growth regulatory, anti-edematogenic, photosystem II inhibitory and photosynthesis uncoupler, and antifungal properties. However, few studies on the antiproliferative profile of compound 1 and/or its derivatives have been reported up to date. Here, we describe the isolation of compound 1 from hexane extract of P. polygalaeflorus fruits as well as the semisynthesis of three lactone derivatives: 6 alpha-hydroxyvouacapan-7 beta,17 beta-lactone (2), 6 alpha-acetoxyvouacapan-7 beta,17 beta-lactone (3), and 6-oxovouacapan-7 beta,17 beta-lactone (4). Additionally, antiproliferative activity of these compounds against nine human cancer cell lines was investigated. Our results revealed that 6 alpha-ahydroxyvouacapan-7 beta,17 beta-lactone (2) was the most potent furanditerpene against all cancer cell lines studied. The presence of non-substituted hydroxyl group at C-6 and the presence of 7 beta,17 beta-lactone ring are important for the antiproliferative activity of these compounds. (C) 2009 Elsevier Inc. All rights reserved.