Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H |
| |
| Authors: | Marchand Christophe Beutler John A Wamiru Antony Budihas Scott Möllmann Ute Heinisch Lothar Mellors John W Le Grice Stuart F Pommier Yves |
| |
| Affiliation: | Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. marchand@nih.gov |
| |
| Abstract: | A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
