Design, synthesis and X-ray crystallographic study of NAmPRTase inhibitors as anti-cancer agents.

Hyun You, Hyung-Seop Youn, Isak Im, Man-Ho Bae, Sang-Kook Lee, Hyojin Ko, Soo Hyun Eom, Yong-Chul Kim

文献索引：Eur. J. Med. Chem. 46 , 1153-1164, (2011)

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摘要

NAmPRTase (PBEF/Visfatin) plays a pivotal role in the salvage pathway of NAD(+) biosynthesis. NAmPRTase has been an attractive target for anti-cancer agents that induce apoptosis of tumor cells via a declining plasma NAD(+) level. In this report, a series of structural analogs of FK866 (1), a known NAmPRTase inhibitor, was synthesized and tested for inhibitory activities against the proliferation of cancer cells and human NAmPRTase. Among them, compound 7 showed similar anti-cancer and enzyme inhibitory activities to compound 1. Further investigation of compound 7 with X-ray analysis revealed a co-crystal structure in complex with human NAmPRTase, suggesting that Asp219 in the active site of the enzyme could contribute to an additional interaction with the pyrrole nitrogen of compound 7.Copyright © 2011 Elsevier Masson SAS. All rights reserved.