Synthesis of Benzocycloalkanone-Based Michael Acceptors and Biological Activities as Antimalarial and Antitrypanosomal Agents.

Abstract

A series of benzocycloalkanone derivatives have been prepared and evaluated as antimalarial and antitrypanosomal agents. The compounds were obtained by direct coupling of preformed 4-substituted benzaldehyde and indanone or tetralone substitutes through aldol condensation of Claisen-Schmidt using sodium hydroxide as a catalyst in ethanol at room temperature. Although designed to inhibit the formation of β-hematin in vitro, only three compounds, 10, 11, and 12, showed activities greater than 50% (75.16%, 63.02%, and 56.17%, respectively). The results of the in vivo antimalarial evaluation show that 10, 11, and 12 reduced parasitemia marginally, and an insignificant increase in the days of survival of the mice was observed. As trypanocidals, all compounds showed marginal activity as inhibitors of the proliferation of T. cruzi epimastigotes, except compound 33, with an activity of 51.08 ± 3.4% compared to the activity shown by the reference compound benznidazole 59.99 ± 2.9%. The compounds appear to have little cytotoxic effect against VERO cells in vitro; this new class of Michael acceptor agents clearly warrants further investigation.