Interaction of novel 3TC prodrugs with the efflux protein P-gp

GUALDESI, S.; BRIÑÓN, M.C.; QUEVEDO, M.A.

Rosario - Argentina

Congreso; 2a Reunión Internacional de Ciencias Farmacéuticas; 2012

Comité de la 2a Reunión Internacional de Ciencias Farmacéuticas

Lamivudine (3TC) is an antiviral drug with widely demonstrated clinical efficacy. However, the emergence of resistant viral strains has limited its effect, and so several strategies have been envisioned to optimize its pharmacotherapeutic properties. The design of prodrugs is a recognized approach to reach this goal. In line with this, we have previously reported results concerning the intestinal permeability of 3TC-Etha and 3TC-Buta, two novel 3TC prodrugs, in which 3TC-Etha was subjected to P-glycoprotein (P-gp) mediated efflux in the intestine, while 3TC-Buta was not. Based on these reports, the objective of this work is to identify the structural basis of this selective recognition by applying molecular modeling methods.