1. Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase.
- Author
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Shengjun Wang, Wenjie Zhu, Xuan Wang, Jianguo Li, Kehui Zhang, Liangren Zhang, Yong-Juan Zhao, Hon Cheung Lee, and Lihe Zhang
- Subjects
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NICOTINAMIDE adenine dinucleotide phosphate , *CHEMICAL synthesis , *RIBOSE , *CALCIUM , *COENZYMES , *CYCLIC compounds - Abstract
Nicotinamide adenine dinucleotide (NAD), one of the most important coenzymes in the cells, is a substrate of the signaling enzyme CD38, by which NAD is converted to a second messenger, cyclic ADP-ribose, which releases calcium from intracellular calcium stores. Starting with 2'-deoxy-2'-fluoroarabinosyl-β-nicotinamide adenine dinucleotide (ara-F NAD), a series of NAD analogues were synthesized and their activities to inhibit CD38 NAD glycohydrolase (NADase) were evaluated. The adenosine-modified analogues showed potent inhibitory activities, among which 2'-deoxy-2'-fluoroarabinosyl-β-nicotinamide guanine dinucleotide (ara-F NGD) was the most effective one. The structure-activity relationship of NAD analogues was also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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