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获得性免疫缺陷综合征(艾滋病)的化疗:无环核苷膦酸类似物。

Chemotherapy of the acquired immune deficiency syndrome (AIDS): acyclic nucleoside phosphonate analogues.

作者信息

De Clercq E

机构信息

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

出版信息

Int J Immunopharmacol. 1991;13 Suppl 1:91-8. doi: 10.1016/0192-0561(91)90130-y.

Abstract

The acyclic nucleoside phosphonate analogues (HPMPA, HPMPC, PMEA, FPMPA) show great promise for the treatment of infections with such important human pathogens as adeno, pox (vaccinia) and hepadna (hepatitis B) viruses (HPMPA), herpes (herpes simplex, varicella-zoster, cytomegalo, Epstein-Barr) viruses (HPMPC), and retro (human immunodeficiency) viruses (PMEA, FPMPA). All these compounds seem to be targeted at the viral DNA polymerase, with which they interact, as either competitive inhibitors or alternative substrates (or chain terminators), following their intracellular phosphorylation to the diphosphoryl derivatives. Of particular interest is the prolonged anti-viral action, lasting for several days or even weeks, that has been noted both in vitro and in vivo after a single administration of the acyclic nucleoside phosphonates.

摘要

无环核苷膦酸酯类似物(HPMPA、HPMPC、PMEA、FPMPA)在治疗由重要人类病原体引起的感染方面显示出巨大潜力,这些病原体包括腺病毒、痘病毒(牛痘)和嗜肝DNA病毒(乙型肝炎病毒)(HPMPA)、疱疹病毒(单纯疱疹病毒、水痘 - 带状疱疹病毒、巨细胞病毒、EB病毒)(HPMPC)以及逆转录病毒(人类免疫缺陷病毒)(PMEA、FPMPA)。所有这些化合物似乎都作用于病毒DNA聚合酶,在细胞内磷酸化成为二磷酸衍生物后,它们作为竞争性抑制剂或替代底物(或链终止剂)与该酶相互作用。特别值得关注的是,单次给予无环核苷膦酸酯后,在体外和体内均观察到其具有持续数天甚至数周的延长抗病毒作用。

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