EVALUATION AND SYNTHESIS OF AZT PRODRUGS WITH OPTIMIZED CHEMICAL STABILITIES. EXPERIMENTAL AND THEORETICAL ANALYSES

RIBONE, S. R.; SCHENFELD, E.; MADRID, M.; PIERINI, A.; QUEVEDO, M. A.

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2015

!--[if gte mso 9]> The design of prodrugs of nucleoside reversetranscriptase inhibitors (NRTIs) constitutes a promising strategy to overcomeseveral suboptimal pharmacotherapeutic properties of these kinds of drugs,among which zidovudine (AZT) is the most studied example. The chemicalstability of prodrugs is a critical issue in the context of their pharmacotherapeuticperformance since it constitutes a key event in the reconversion of thebioactive NRTIs. In this study, five prodrugs of AZT and lamivudine (3TC) werestudied by means of DFT and classical molecular dynamics (MD) strategies inorder to model the reaction coordinates involved in their chemical hydrolysis, andextend these conclusions to further structure rationalization