USE OF PHARMACO-MODULATION STRATEGIES IN THE SEARCH OF 1,8-CINEOLE DERIVATIVES WITH HIGHER LEISHMANICIDAL ACTIVITY

MURO AC; GÁLVEZ C; VILLECCO MB; GARRIDO J; PARRAVICINI O; LOANDOS MH

Jornada; TUCUMAN BIOLOGY ASSOCIATION. XXXIV ANNUAL SCIENTIFIC MEETING.; 2017

1,8-cineol, also known as eucalyptol, is a monoterpene widely distributed in nature. It is present in more than 200 pharmaceutical formulations due to its decongestant, antitussive, antiinflammatory and antiparasitic properties. In previous works we described the leishmanicidal activity of 9-hydroxycineol (1) with encouraging results. In this work, in order to favorably modify the biological activity of 1, the synthesis of a homologous series of 9-hydroxycinineol with saturated monocarboxylic acids (C2→C9) was carried out, using homology as a pharmacomodulation strategy for the structural optimization of the lead compound. In vitro leishmanicidal effects on promastigotes and intracellular amastigotes of Leishmania infantum and L. donovani were also studied. The antiparasitic activity assays showed that the increase in the carbon chain length of the homologous esters synthesized caused reduction of 70-80% in the multiplication of promastigotes. Against intracellular amastigotes, most compunds managed to eliminate almost all of parasites, probably due to the increased lipophilicity of these derivatives. Thus, the use of homology as a modulation strategy was very useful for the design and synthesis of 1,8-cineol derivatives with improved bioogical activity and bioavailability, this being a convenient alternative for the obtainment of new leishmanicidal agents.