Anti-leishmanial activity of neolignans from Virola species and synthetic analogues

Surinamensin, a neolignan isolated from Virola surinamensis, 3,4,5-trimetho xy-8-[2',6'-dimethoxy-4'-(E)-prophenylphenoxy]phenylpropane, a neolignan is olated from Virola pavonis, and 25 of its synthetic analogues or correlated substances with ether linkages and their corresponding C-8 sulphur and nit rogen analogues, were tested for activity against Leishmania donovani amast igotes and promastigotes in vitro. Some were active against L. donovani pro mastigotes at 30 muM but inactive against intracellular amastigotes. The na tural neolignan from V. pavonis was active against promastigotes at 100 muM . The highest selective activity was found in those compounds with sulphur bridges. The beta -ketosulfide (3,4-dimethoxy)-8-(4'-methylthiophenoxy) pro duced 42% inhibition of L. donovani amastigotes in the liver of BALB/c mice at 100 mg/kg given once daily for five consecutive days (P > 0.05). (C) 20 00 Elsevier Science Ltd. All rights reserved.