Prenylated pterocarpans as bacterial neuraminidase inhibitors

During the course of a neuraminidase inhibitor screening program on natural products, four new (6, 8, 11, and 12) and eleven known (1-5, 7, 9-10, and 13-15) pterocarpan derivatives were isolated as active principles from the EtOAc extract of the stem bark of Erythrina abyssinica. Their structures were identified by spectroscopic data analyses. All isolates exhibited significant inhibitory effects on the neuraminidases from Clostridium perfringens and Vibrio cholerae with IC(50) values ranging from 1.32 to 77.10 mu M and 0.35 to 77.73 mu M, respectively. The isolates (1-3, 5-8, 10, and 13-15), which possessed noncompetitive inhibition modes in kinetic studies, showed stronger activity against C. perfringens neuraminidase (IC(50) 1.32-19.82 mu M) than quercetin (IC(50) 25.34 mu M), which was used as the positive control. In contrast, compounds 4 and 9 behaved as competitive inhibitors and were displayed less effective (IC(50) 26.39-33.55 mu M). Furthermore, calopocarpine, as a neuraminidase inhibitor, produced a decrease of V. cholerae adhesion to the host cell. Overall, these results suggest that neuraminidase inhibitors can be used in the development of new treatments to combat infectious diseases. (C) 2010 Elsevier Ltd. All rights reserved.