Inhibition of HIV-1 protease and RNase H of HIV-1 reverse transcriptase activities by long chain phenols from the sarcotestas of Ginkgo biloba.
Nine long-chain phenols: four cardanols (1-4), two bilobols (5, 6) and three alkylsalicylic acids (7-9) [corrected] were isolated from the CH(2)Cl(2) extracts of the sarcotestas of Ginkgo biloba as HIV-1 protease (PR) inhibitors. From these phenols, the bilobols (IC (50), 2.6 - 5.8 microM) and alkylsalicylic acids (IC (50), 10.2 - 24.9 microM) exhibited dose-dependent potent inhibitory activities on HIV-1 PR, while the cardanols did not. On the other hand, only the alkylsalicylic acids (IC (50), 33.7 - 170.3 microM) inhibited the activities of RNase H of HIV-1 reverse transcriptase (RT), while all of the compounds failed to affect the RNA dependent DNA polymerase (RDDP) of HIV-1 RT. Therefore, we regard bilobols as a new class and selective inhibitors of HIV-1 PR; in addition, alkylsalicylic acids are elucidated as a new class of inhibitors against HIV-1 PR and RNase H of HIV-1 RT.
Lee
Ji Suk
JS
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 599 Kwanangno, Kwanak-gu, Seoul, Korea. jslee103@snu.ac.kr
Hattori
Masao
M
Kim
Jinwoong
J
D020441:Ginkgo biloba / Q000737:chemistry*; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D054309:Ribonuclease H, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors
D017320:HIV Protease Inhibitors; D010636:Phenols; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D054309:Ribonuclease H, Human Immunodeficiency Virus; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1