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Structure activity relationship studies of natural product chemokine receptor CCR5 antagonist anibamine toward the development of novel anti prostate cancer agents.

Abstract：

:Recent studies have indicated that the CCR5 chemokine receptor may be a potential target for treating prostate cancer. Thus, development of CCR5 antagonists may provide novel prostate cancer therapy. Anibamine, a novel pyridine quaternary alkaloid isolated from Aniba sp., was found to effectively compete with (125)I-gp120 in binding to the chemokine receptor CCR5, with an IC(50) = 1 μM. Anibamine is the first natural product reported as a CCR5 antagonist, and thus provides a novel structural skeleton unique from other lead compounds that have generally been identified from high-throughput screening efforts. In order to refine the lead compound's structure and improve the therapeutic index of anibamine derivatives as potential anti prostate cancer agents, the approach of "deconstruction-reconstruction-elaboration" was applied in the structure-activity relationship studies of this work. Here, we report the design, syntheses and anti prostate cancer activities of anibamine and 17 analogues. The results from the in vitro and in vivo studies described here show that this class of compounds has potential to provide novel leads as anti prostate cancer agents.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang F,Arnatt CK,Haney KM,Fang HC,Bajacan JE,Richardson AC,Ware JL,Zhang Y

doi

10.1016/j.ejmech.2012.07.049

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

395-408

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(12)00475-8

journal_volume

55

pub_type

杂志文章

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