Surinamensin, a neolignan isolated from Virola surinamensis, 3,4,5-trimethoxy-8-[2',6'-dimethoxy-4'-(E)-prophenylphenoxy]phenylpropane, a neolignan isolated from Virola pavonis, and 25 of its synthetic analogues or correlated substances with ether linkages and their corresponding C-8 sulphur and nitrogen analogues, were tested for activity against Leishmania donovani amastigotes and promastigotes in vitro. Some were active against L. donovani promastigotes at 30 muM but inactive against intracellular amastigotes. The natural 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) produced 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) 2000 Elsevier Science Ltd. All rights reserved.556589595