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Article: Synthesis and biological evaluation of nicotinamide adenine dinucleotides analogues as inhibitors of CD38

TitleSynthesis and biological evaluation of nicotinamide adenine dinucleotides analogues as inhibitors of CD38
Authors
KeywordsBiological Activity
Cd38 Inhibitor
Fluoro-Substituted Nad Analogue
Nicotinamide Adenine Dinucleotides(Nad)
Issue Date2012
PublisherJilin Daxue. The Journal's web site is located at http://www.cjcu.jlu.edu.cn/
Citation
Gaodeng Xuexiao Huaxue Xuebao/Chemical Journal Of Chinese Universities, 2012, v. 33 n. 6, p. 1226-1232 How to Cite?
AbstractCD38 is the main mammalian ADP-ribosyl cyclase and a signaling enzyme responsible for catalyzing the synthesis of Ca 2+-messengers and plays a critical role in a wide range of physiological functions. It is of great interest to develop specific and generally applicable inhibitors of CD38. Fluoro-substituted nicotina-mide adenine dinucleotides(NAD), such as ara-F NMN and ara-F NAD, are catalysis-dependent inhibitors of CD38 and are often used as probes for investigating the function of CD38. For understanding the effect of fluoro-substitution on activity in more detail and discovery of active inhibitors of CD38, compounds 2a-2c were synthesized and their inhibition against the hydrolysis activities of CD38 were evaluated. The syntheses were performed by starting from the corresponding fluoro-substituted sugar, then followed by coupling with nicoti-namide, regio-selective 5′-phosphorylation and condensation with adenosine monophosphate, successively. All target compounds were purified by HPLC and characterized by NMR and HRMS. Two compounds showed strong inhibitions, especially 2′-deoxy-2′-fluororibonofuranosyl which gave activity with IC 50 of 0.056 μmol/L and was two orders of magnitude higher than positive control ara-F NAD. The results also showed that the activity was greatly affected by the number and the position of fluorine atom on the sugar ring, as well as the configuration of the inhibitors. The detailed biological investigation and structure-activity relationship are underway.
Persistent Identifierhttp://hdl.handle.net/10722/171795
ISSN
2014 Impact Factor: 0.799
2014 SCImago Journal Rankings: 0.210
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Zen_US
dc.contributor.authorKwong, AKYen_US
dc.contributor.authorYang, ZJen_US
dc.contributor.authorZhang, LRen_US
dc.contributor.authorLee, HCen_US
dc.contributor.authorZhang, LHen_US
dc.date.accessioned2012-10-30T06:17:10Z-
dc.date.available2012-10-30T06:17:10Z-
dc.date.issued2012en_US
dc.identifier.citationGaodeng Xuexiao Huaxue Xuebao/Chemical Journal Of Chinese Universities, 2012, v. 33 n. 6, p. 1226-1232en_US
dc.identifier.issn0251-0790en_US
dc.identifier.urihttp://hdl.handle.net/10722/171795-
dc.description.abstractCD38 is the main mammalian ADP-ribosyl cyclase and a signaling enzyme responsible for catalyzing the synthesis of Ca 2+-messengers and plays a critical role in a wide range of physiological functions. It is of great interest to develop specific and generally applicable inhibitors of CD38. Fluoro-substituted nicotina-mide adenine dinucleotides(NAD), such as ara-F NMN and ara-F NAD, are catalysis-dependent inhibitors of CD38 and are often used as probes for investigating the function of CD38. For understanding the effect of fluoro-substitution on activity in more detail and discovery of active inhibitors of CD38, compounds 2a-2c were synthesized and their inhibition against the hydrolysis activities of CD38 were evaluated. The syntheses were performed by starting from the corresponding fluoro-substituted sugar, then followed by coupling with nicoti-namide, regio-selective 5′-phosphorylation and condensation with adenosine monophosphate, successively. All target compounds were purified by HPLC and characterized by NMR and HRMS. Two compounds showed strong inhibitions, especially 2′-deoxy-2′-fluororibonofuranosyl which gave activity with IC 50 of 0.056 μmol/L and was two orders of magnitude higher than positive control ara-F NAD. The results also showed that the activity was greatly affected by the number and the position of fluorine atom on the sugar ring, as well as the configuration of the inhibitors. The detailed biological investigation and structure-activity relationship are underway.en_US
dc.languageengen_US
dc.publisherJilin Daxue. The Journal's web site is located at http://www.cjcu.jlu.edu.cn/en_US
dc.relation.ispartofGaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universitiesen_US
dc.subjectBiological Activityen_US
dc.subjectCd38 Inhibitoren_US
dc.subjectFluoro-Substituted Nad Analogueen_US
dc.subjectNicotinamide Adenine Dinucleotides(Nad)en_US
dc.titleSynthesis and biological evaluation of nicotinamide adenine dinucleotides analogues as inhibitors of CD38en_US
dc.typeArticleen_US
dc.identifier.emailLee, HC:leehc@hku.hken_US
dc.identifier.authorityLee, HC=rp00545en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.3969/j.issn.0251-0790.2012.06.018en_US
dc.identifier.scopuseid_2-s2.0-84864385576en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84864385576&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume33en_US
dc.identifier.issue6en_US
dc.identifier.spage1226en_US
dc.identifier.epage1232en_US
dc.identifier.isiWOS:000305819100018-
dc.publisher.placeChinaen_US
dc.identifier.scopusauthoridChen, Z=37033573500en_US
dc.identifier.scopusauthoridKwong, AKY=54932929500en_US
dc.identifier.scopusauthoridYang, ZJ=7405435277en_US
dc.identifier.scopusauthoridZhang, LR=8833065300en_US
dc.identifier.scopusauthoridLee, HC=26642959100en_US
dc.identifier.scopusauthoridZhang, LH=10340097000en_US

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