Akintonwa Dunstan A A
Centre for Theoretical Mechanistic Biochemistry, Amazing Grace, Calabar, Cross River State, Nigeria.
Med Hypotheses. 2002 Dec;59(6):622-5. doi: 10.1016/s0306-9877(02)00146-9.
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. Therefore for toxic effects the trend is AZT(5+) > ddc(3+) > At(0). TMB efficacy of AZT was based on the generations of *OH from the 1-NH (1+) and the 3(1)-azido (N(3))(1+) and azide free radical (*N(3)), (1+) totalling 3+ compared with ddc of 1+ and At of 1+. Therefore for efficacy, the trend is AZT(3+) > ddc(1+) = At(1+). In combination drug therapy, TMB postulates the following for HIV : AIDS: At(1+) + AZT(3+) + ddc(1+) > AZT(3+) + ddc(1+) = AZT(3+) + At(1+) > AZT(3+) > At(1+) + ddc(1+) > ddc(1+) = At(1+).
基于叠氮胸苷（AZT）的结构和人类免疫缺陷病毒（HIV）的结构，通过理论机制生物化学（TMB）技术评估了AZT对人类免疫缺陷病毒的毒性作用和疗效。AZT的环氧化物呈阳性（1+）；羟基自由基（*OH）呈阳性（2+）；（*N(3)）叠氮自由基呈阳性（1+），叠氮化物（N(3-)）生成呈阳性（1+）。AZT的芳烃亚胺和亚硝基生成呈阴性（-），与双脱氧胞苷（ddc）的3+和青蒿琥酯（At）的0相比，总毒性作用为5+。因此，就毒性作用而言，趋势是AZT(5+) > ddc(3+) > At(0)。AZT的TMB疗效基于1-NH（1+）、3(1)-叠氮基（N(3)）（1+）和叠氮自由基（N(3)）（1+）生成的OH，与ddc的1+和At的1+相比，总生成量为3+。因此，就疗效而言，趋势是AZT(3+) > ddc(1+) = At(1+)。在联合药物治疗中，TMB对HIV提出以下假设：艾滋病：At(1+) + AZT(3+) + ddc(1+) > AZT(3+) + ddc(1+) = AZT(3+) + At(1+) > AZT(3+) > At(1+) + ddc(1+) > ddc(1+) = At(1+) 。
