Theoretical mechanistic basis of the toxic effects and efficacy of dideoxycytidine in HIV:AIDS.

Abstract

Based on the structure of dideoxycytidine (ddc), the toxic effects of nitroso, areneimine, epoxide, hydroxyl free radical (*OH) and calcium chelating propensity respectively were evaluated using theoretical mechanistic biochemistry techniques. The 4-NH(2)group of the pyrimidine ddc structure was positive (+) for nitroso, (+) for areneimine, (+) for *OH; (+) for epoxide and negative (-) for calcium chelating propensity TMB toxic effects. The *OH was used to evaluate the TMB efficacy of ddc based on the structure of HIV. The *OH was found to be capable of damaging each of the following of the HIV structure: (1) the outer lipid membrane; (2) the glycoproteins of the envelope; (3) the viral RNA; (4) the p18 and p24 proteins in the core of the virus and (5) the reverse transcriptase replicating enzyme. The *OH is, therefore, exhibiting the characteristics of a 'bullet exterminator' for HIV:AIDS by attacking from the outwards inwards. Combination therapy of Artesunate (At) + AZT + ddc > At + AZT > AZT + ddc = At + ddc in the efficacy of HIV:AIDS was postulated.

• Authors: D A Akintonwa
• Journal: Medical hypotheses (Med Hypotheses) Vol. 57 Issue 2 Pg. 249-51 (Aug 2001) ISSN: 0306-9877 [Print] United States
• PMID: 11461183 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Harcourt Publishers Ltd.

Chemical References

• Anti-HIV Agents
• Reverse Transcriptase Inhibitors
• Zalcitabine

Topics

• Anti-HIV Agents (adverse effects, pharmacology, therapeutic use)
• HIV Infections (drug therapy)
• Humans
• Models, Theoretical
• Reverse Transcriptase Inhibitors (adverse effects, pharmacology, therapeutic use)
• Zalcitabine (adverse effects, pharmacology, therapeutic use)