De Clercq E, Yamamoto N, Pauwels R, Baba M, Schols D, Nakashima H, Balzarini J, Debyser Z, Murrer B A, Schwartz D
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5286-90. doi: 10.1073/pnas.89.12.5286.
A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains in various human T-cell systems, including peripheral blood lymphocytes, at 0.14-1.4 microM, without being toxic to the host cells at 2.2 mM. The bicyclam JM2763 is active against 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant HIV-1 strains and acts additively with AZT. Mechanism of action studies revealed that the bicyclams (i.e., JM2763) interact with an early event of the retrovirus replicative cycle, which could be tentatively identified as a viral uncoating event.
一系列双环胺已被证明是人类免疫缺陷病毒（HIV）的有效且选择性抑制剂。这些化合物在0.14 - 1.4微摩尔浓度下，对包括外周血淋巴细胞在内的各种人类T细胞系统中的多种HIV - 1和HIV - 2毒株的复制具有抑制作用，而在2.2毫摩尔浓度下对宿主细胞无毒。双环胺JM2763对3'-叠氮-3'-脱氧胸苷（齐多夫定；AZT）耐药的HIV - 1毒株具有活性，并且与AZT具有相加作用。作用机制研究表明，双环胺（即JM2763）与逆转录病毒复制周期的早期事件相互作用，这一事件初步可确定为病毒脱壳事件。
