基于生物电子等排原理的核苷类HIV-1逆转录酶抑制剂研究进展

Review of the study of structure modification of HIV NRTIs on the principles of bioisosterism

核苷类HIV逆转录酶抑制剂(NRTIs)作为逆转录酶的特异性抑制剂,是临床最早应用的一类抗HIV药物,至今仍发挥着重要的作用。NRTIs的应用有效地缓解症状,延长病程,对治疗AIDS有很好的效果。然而由于耐药毒株及毒副作用的出现,NRTIs的疗效受到很大限制,因此研发高效、低毒、耐突变的新型NRTIs仍然是目前的热点之一。通过生物电子等排原理对核苷类药物进行广泛的结构修饰是获得高效、低毒、具有较高生物利用度的新型药物的有效途径。本文综述了该领域的研究进展。

HIV nucleoside reverse transcriptase inhibitors （NRTIs）,as a kind of specific reverse transcriptase inhibitors and the earliest clinical applications of anti-HIV drugs, are still playing an important role. In the treatment of AIDS, NRTIs can effectively alleviate the symptoms and extend the duration. However, because of the drug-resistant strains and the toxico- logical side-effects,the efficacy of NRTIs has been greatly restricted. So R ＆ D,a new type of NRTIs which has high efficiency, low toxicity and resistance mutations,is still one of the most widely applied in the present time. By the principles of the bioisos- terism,the comprehensive structure modification of nucleoside drugs is an efficient way to develop a new drug with low toxin, high bioavailability and powerful effect. This paper is an attempted review of the study and research in this field.