- Design, synthesis and X-ray crystallographic study of NAmPRTase inhibitors as anti-cancer agents
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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.
- You, Hyun,Youn, Hyung-Seop,Im, Isak,Bae, Man-Ho,Lee, Sang-Kook,Ko, Hyojin,Eom, Soo Hyun,Kim, Yong-Chul
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experimental part
p. 1153 - 1164
(2011/04/17)
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- FAB I INHIBITORS
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Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.
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- Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI)
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Bacterial enoyl-ACP reductase (FabI) catalyzes the final step in each cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents. Our efforts to identify potent, selective FabI inhibitors began w
- Miller, William H.,Seefeld, Mark A.,Newlander, Kenneth A.,Uzinskas, Irene N.,Burgess, Walter J.,Heerding, Dirk A.,Yuan, Catherine C. K.,Head, Martha S.,Payne, David J.,Rittenhouse, Stephen F.,Moore, Terrance D.,Pearson, Stewart C.,Berry, Valerie,DeWolf Jr., Walter E.,Keller, Paul M.,Polizzi, Brian J.,Qiu, Xiayang,Janson, Cheryl A.,Huffman, William F.
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p. 3246 - 3256
(2007/10/03)
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