Favorable interaction of beta-L(-) nucleoside analogues with clinically approved anti-HIV nucleoside analogues for the treatment of human immunodeficiency virus

Biochemical Pharmacology
E G BridgesY C Cheng

Abstract

The combination of L(-)-2',3'-dideoxy-3'-thiacytidine (L(-)SddC, 3TC), L(-)-2',3'-dideoxy-5-fluorocytidine (L(-)FddC), or L(-)-2',3'-dideoxy-5-fluoro-3'-thiacytidine (L(-)(FTC) with 3'-azido-3'-deoxythymidine (AZT) synergistically inhibited replication of human immunodeficiency virus (HIV) in vitro. Similar synergistic activity was also obtained when these compounds were used in combination with 2',3'-didehyro-2',3'-dideoxythymidine (D4T). In terms of 2',3'- dideoxyinosime (ddI) and 2',3'-dideoxycytidine (ddC), only additive anti-HIV activity was observed. None of the beta-L(-) nucleoside analogues had additive toxicity in cell culture, and they could protect against the delayed mitochondrial toxicity associated with AZT, D4T, ddC, and ddI in drug-treated cells. Thus, combinations of beta-L(-) nucleoside analogues with any of the approved anti-HIV drugs could have a potentially beneficial outcome.

References

Apr 1, 1993·Antimicrobial Agents and Chemotherapy·R F SchinaziJ W Mellors
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T ShirasakaH Mitsuya

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Citations

Jul 29, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·J T LonerganW C Mathews
Dec 3, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Michael S Saag
Apr 24, 2004·Antimicrobial Agents and Chemotherapy·Ginger E DutschmanYung-Chi Cheng
Jun 13, 2001·Sexually Transmitted Infections·A J White
Aug 30, 2008·Antiviral Chemistry & Chemotherapy·Erik De Clercq, Hugh J Field
Jun 7, 2003·Antiviral Chemistry & Chemotherapy·Susan Erickson-ViitanenRaymond F Schinazi
Dec 6, 2002·Drugs·Susan M Cheer, Karen L Goa
Apr 25, 2001·The Journal of Biological Chemistry·S E Lim, W C Copeland
Apr 2, 1999·Antimicrobial Agents and Chemotherapy·L T MartinJ P Sommadossi
Oct 23, 1997·Biochemical Pharmacology·S KewnD J Back

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