info:eu-repo/semantics/article
Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure
Fecha
2002-10Registro en:
Turk, Gabriela Julia Ana; Fernández Moroni, Guillermo; Pampuro, Sandra Esther; Brión, Margarita C.; Salomon, Horacio Eduardo; Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure; Elsevier Science; International Journal of Antimicrobial Agents; 20; 4; 10-2002; 282-288
0924-8579
CONICET Digital
CONICET
Autor
Turk, Gabriela Julia Ana
Fernández Moroni, Guillermo
Pampuro, Sandra Esther
Brión, Margarita C.
Salomon, Horacio Eduardo
Resumen
Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3′-azido-3′-deoxy-5′-O-oxalyl-N-valinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-leucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-isoleucinethymidine, 3′-azido-3′-deoxy-5′-O-oxalyl-N-phenylalaninethymidine, 3′-azido-3′-deoxy-5′-O-oxalylthymidine acid, 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3′-azido-3′-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.