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-NH2group 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.