Singh Sheo B, Ondeyka John G, Schleif William A, Felock Peter, Hazuda Daria J
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
J Nat Prod. 2003 Oct;66(10):1338-44. doi: 10.1021/np030211s.
Integracides, 4,4-dimethylergostane triterpenoids, are inhibitors of HIV-1 integrase, a critical enzyme in replication of HIV-1. The chemistry and structure-activity relationship of integracide B and related natural products are described. A charged group, e.g., a sulfate, carboxyl, or amino, is required for the HIV-1 integrase activity. These compounds showed HIV-1 integrase activity with IC(50) values in the range 4.8-15 muM and exhibited antiviral activity in a viral spread assay, but with only a small or no therapeutic window.
整合杀剂，即4,4-二甲基麦角甾烷三萜类化合物，是HIV-1整合酶的抑制剂，HIV-1整合酶是HIV-1复制过程中的一种关键酶。本文描述了整合杀剂B及相关天然产物的化学性质和构效关系。HIV-1整合酶活性需要一个带电基团，例如硫酸根、羧基或氨基。这些化合物表现出HIV-1整合酶活性，IC(50)值在4.8 - 15 μM范围内，并且在病毒传播试验中表现出抗病毒活性，但治疗窗很小或没有治疗窗。
