Jayasuriya Hiranthi, Herath Kithsiri B, Ondeyka John G, Polishook Jon D, Bills Gerald F, Dombrowski Anne W, Springer Marty S, Siciliano Sal, Malkowitz Lorraine, Sanchez Manuel, Guan Ziqiang, Tiwari Suroojnauth, Stevenson Dennis W, Borris Robert P, Singh Sheo B
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
J Nat Prod. 2004 Jun;67(6):1036-8. doi: 10.1021/np049974l.
Human CCR5 is a G-coupled receptor that binds to the envelope protein gp120 and CD4 and mediates the HIV-1 viral entry into the cells. The blockade of this binding by a small molecule receptor antagonist could lead to a new mode of action agent for HIV-1 and AIDS. Screening of natural product extracts led to the identification of anibamine (1), a novel pyridine quaternary alkaloid as a TFA salt, from Aniba sp.; ophiobolin C from fermentation extracts of fungi Mollisia sp.; and 19,20-epoxycytochalasin Q from Xylaria sp. Formation of the TFA salt of anibamine is plausibly an artifact of the isolation. The identity of the natural counterion is unknown. Anibamine.TFA competed for the binding of 125I-gp120 to human CCR5 with an IC50 of 1 microM. Ophiobolin C and 19,20-epoxycytochalasin Q exhibited binding IC50) values of 40 and 60 microM, respectively.
人CCR5是一种G蛋白偶联受体，它与包膜蛋白gp120和CD4结合，并介导HIV-1病毒进入细胞。小分子受体拮抗剂对这种结合的阻断可能会产生一种针对HIV-1和艾滋病的新型作用药物。对天然产物提取物的筛选导致从樟科植物中鉴定出一种新型吡啶季铵生物碱阿尼巴明（1），其为三氟乙酸盐；从真菌柔膜菌属的发酵提取物中鉴定出蛇孢菌素C；从炭角菌属中鉴定出19,20-环氧细胞松弛素Q。阿尼巴明三氟乙酸盐的形成可能是分离过程中的人为产物。天然抗衡离子的身份未知。阿尼巴明·三氟乙酸盐以1微摩尔/升的半数抑制浓度（IC50）竞争125I-gp120与人CCR5的结合。蛇孢菌素C和19,20-环氧细胞松弛素Q的结合半数抑制浓度（IC50）值分别为40和60微摩尔/升。
