Theoretical mechanistic basis of the toxic effects and efficacy of dideoxycytidine in HIV:AIDS.
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.
Akintonwa
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Centre for Theoretical Mechanistic Biochemistry, PO Box 3129, Calabar, Cross River State, Nigeria.
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008962:Models, Theoretical; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016047:Zalcitabine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine