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

Toxic effects and efficacy of azidothymidine (AZT) in human immunodeficiency virus were evaluated by theoretical mechanistic biochemistry (TMB) techniques based on the structure of AZT and on the structure of HIV. AZT was positive (1+) for epoxide; (2+) for hydroxl free radical (*OH); (1+) for (*N(3)) azide free radical and (1+) for azide (N(3-)) generations, respectively. AZT was negative (-) for areneimine, and nitroso generations, respectively, for toxic effects totalling 5+ compared with dideoxycytidine (ddc) of 3+ and artesunate (At) of 0.

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.

Correlation between predicted theoretical mechanistic biochemistry (TMB) data and therapeutic effects in the management of vascular disorders with calcium channel blockers.

Theoretical mechanistic biochemistry (TMB) analysis was used to predict the therapeutic effects of calcium channel blockers in the drug management of hypertension, cerebrovascular disorders (CVD) and coronary artery disease (CAD). This analysis was extended to acetylsalicylic acid (aspirin) a non-calcium channel blocker which is nevertheless commonly used in the management of the same disorders. TMB data have suggested nisoldipine, nicardipine and nimodipine as agents of choice in the management of cerebrovascular disease, e.

Theoretical mechanistic basis of oxidants of methaemoglobin formation.

The mechanism of oxidation or reduction using the electron method was investigated for (I) aniline; (II) nitrobenzene; (III) nitrate; (IV) sulphanilamide; (V) hydrogen peroxide; (VI) hydroxyl free radical; (VII) ferricyanide; (VIII) acetylphenylhydrazine; (IX) nitrite; (X) chlorate and (XI) hydroxylamine respectively. Substances (II), (III), (V), (VI), (VII), (IX), (X) and (XI) evolved as oxidants, with (II), nitrobenzene and (X), chlorate as the most powerful oxidants (number of moles of HbFe(2+)(haemoglobin) of 6 reacting with 1.0 mole of the substance).

The development of an assay for determination of monooxygenase of human foetal livers based on rate of decrease in substrate concentration.

A simple monooxygenase assay based on the rate of decrease in the concentration of the substrate "supona' [2-chloro-1(2,4-dichlorophenyl)vinyl diethyl phosphate] (1) was investigated spectrophotometrically at E246nm in the presence of oxygen and NADPH without the enzyme. The assay was found reliable for incubations at 37 degrees C for periods up to 10 minutes. Incubations in excess of 10 minutes were unreliable due to an unexpected increase in E246nm.