CHEMICAL HYDROLYSIS OF ZIDOVUDINE PRODRUGS: CORRELATION BETWEEN EXPERIMENTAL AND THEORETICAL STUDIES

SCHENFELD ESTEBAN M; RIBONE SERGIO R.; PIERINI A.; QUEVEDO M. ALFREDO

Córdoba

Congreso; Reunión Anual de Ciencia Farmacéuticas 2014 (RICiFa); 2014

FCQ-UNC

Chemical hydrolysis of zidovudine prodrugs: correlation between experimental and theoretical studies The design of prodrugs of zidovudine (AZT) allows the optimization of its pharmacotherapeutic properties, among which acidic prodrugs encompasses the main potential to reach optimized biodistributions. Considering that an adequate chemical stability constitutes a critical property of a prodrug, in this work we present a structure-stability relationship for a serie of AZT prodrugs obtained by esterification with the following acids: oxalic (AZT-Ox), succinic (AZT-Suc), glutaric (AZT-Glu) and adipic (AZT-Adi). A relationship between experimental assays and molecular modeling techniques is established. Experimental findings: the chemical hydrolysis was measured incubating AZT prodrugs in solutions at various pH, with analytical measurements being performed using an HPLC-UV technique. The rate of hydrolysis was dependent on the pH and molecular structure involved. Half-life times (t1/2) under acidic conditions (pH=2) are: AZT-Ox (21.2 hs)