Isolation and structure of antagonists of chemokine receptor (CCR5)

被引：79

作者：

Jayasuriya, H

Herath, KB

Ondeyka, JG

Polishook, JD

Bills, GF

Dombrowski, AW

Springer, MS

Siciliano, S

Malkowitz, L

Sanchez, M

Guan, ZQ

Tiwari, S

Stevenson, DW

Borris, RP

Singh, SB

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

[2] Merck Sharp & Dohme Ltd, CIBE, Madrid 28027, Spain

[3] New York Bot Garden, Inst Econ Bot, Bronx, NY 10458 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2004年 / 67卷 / 06期

关键词：

D O I：

10.1021/np049974l

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

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 I-125-gp120 to human CCR5 with an IC50 Of 1 muM. Ophiobolin C and 19,20-epoxycytochalasin Q exhibited binding IC50 values of 40 and 60 muM, respectively.

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页码：1036 / 1038

页数：3

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