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Article: Synthesis and biological evaluation of nicotinamide adenine dinucleotides analogues as inhibitors of CD38
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TitleSynthesis and biological evaluation of nicotinamide adenine dinucleotides analogues as inhibitors of CD38
 
AuthorsChen, Z2
Kwong, AKY1
Yang, ZJ2
Zhang, LR2
Lee, HC1
Zhang, LH2
 
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/
 
CitationGaodeng Xuexiao Huaxue Xuebao/Chemical Journal Of Chinese Universities, 2012, v. 33 n. 6, p. 1226-1232 [How to Cite?]
DOI: http://dx.doi.org/10.3969/j.issn.0251-0790.2012.06.018
 
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.
 
ISSN0251-0790
2013 Impact Factor: 0.954
2013 SCImago Journal Rankings: 0.247
 
DOIhttp://dx.doi.org/10.3969/j.issn.0251-0790.2012.06.018
 
ISI Accession Number IDWOS:000305819100018
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChen, Z
 
dc.contributor.authorKwong, AKY
 
dc.contributor.authorYang, ZJ
 
dc.contributor.authorZhang, LR
 
dc.contributor.authorLee, HC
 
dc.contributor.authorZhang, LH
 
dc.date.accessioned2012-10-30T06:17:10Z
 
dc.date.available2012-10-30T06:17:10Z
 
dc.date.issued2012
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationGaodeng Xuexiao Huaxue Xuebao/Chemical Journal Of Chinese Universities, 2012, v. 33 n. 6, p. 1226-1232 [How to Cite?]
DOI: http://dx.doi.org/10.3969/j.issn.0251-0790.2012.06.018
 
dc.identifier.doihttp://dx.doi.org/10.3969/j.issn.0251-0790.2012.06.018
 
dc.identifier.epage1232
 
dc.identifier.isiWOS:000305819100018
 
dc.identifier.issn0251-0790
2013 Impact Factor: 0.954
2013 SCImago Journal Rankings: 0.247
 
dc.identifier.issue6
 
dc.identifier.scopuseid_2-s2.0-84864385576
 
dc.identifier.spage1226
 
dc.identifier.urihttp://hdl.handle.net/10722/171795
 
dc.identifier.volume33
 
dc.languageeng
 
dc.publisherJilin Daxue. The Journal's web site is located at http://www.cjcu.jlu.edu.cn/
 
dc.publisher.placeChina
 
dc.relation.ispartofGaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universities
 
dc.relation.referencesReferences in Scopus
 
dc.subjectBiological Activity
 
dc.subjectCd38 Inhibitor
 
dc.subjectFluoro-Substituted Nad Analogue
 
dc.subjectNicotinamide Adenine Dinucleotides(Nad)
 
dc.titleSynthesis and biological evaluation of nicotinamide adenine dinucleotides analogues as inhibitors of CD38
 
dc.typeArticle
 
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<contributor.author>Lee, HC</contributor.author>
<contributor.author>Zhang, LH</contributor.author>
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<description.abstract>CD38 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&#8242;-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&#8242;-deoxy-2&#8242;-fluororibonofuranosyl which gave activity with IC 50 of 0.056 &#956;mol/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.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Peking University