DICP OpenIR
Characterization of regio- and stereo-selective sulfation of bufadienolides: exploring the mechanism and providing insight into the structure-sulfation relationship by experimentation and molecular docking analysis
Ning, Jing1; Cui, Yonglei1; Wang, Chao1,3,4; Dong, Peipei1; Ge, Guangbo2; Tian, Xiangge1; Hou, Jie1; Huo, Xiaokui1; Zhang, Baojing1; Ma, Tonghui5; Ma, Xiaochi1,3,4
Source PublicationRSC ADVANCES
2016
ISSN2046-2069
DOI10.1039/c5ra22153f
Volume6Issue:7Pages:5774-5783
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences
WOS SubjectChemistry, Multidisciplinary
WOS Research AreaChemistry
WOS KeywordHUMAN DEHYDROEPIANDROSTERONE SULFOTRANSFERASE ; FLIGHT MASS-SPECTROMETRY ; ESTROGEN SULFOTRANSFERASE ; NA+/K+-ATPASE ; STEROIDS ; METABOLISM ; SUBSTRATE ; PHARMACOKINETICS ; CINOBUFACINI ; INHIBITION
AbstractBufadienolides are a major class of bioactive compounds derived from amphibian skin secretion. Recent studies demonstrate that bufadienolides have a promising role in targeted cancer chemotherapy. However, extensive metabolism and inactivation strongly restrict the clinical applications of bufadienolides. This study aimed to systematically characterize the sulfation of six representative bufadienolides (including bufalin, resibufogenin, cinobufagin, bufotalin, telocinobufagin and deacetylcinobufagin) in amphibian skin secretion and to provide insight into the structure-sulfation relationship by experimentation and molecular docking analysis with series of bufadienolides and derivatives. For all the six representative bufadienolides, one corresponding monosulfate was detected in the incubation mixtures. The sulfates were accurately identified as bufadienolides 3-O-sulfates by NMR and HPLC-MSn techniques. Reaction phenotyping studies using human recombinant sulfotransferase (SULT) and liver S9 demonstrated that SULT2A1 mediated the formation of bufadienolide 3-O-sulfate with a high specific selectivity. Further kinetic evaluation demonstrated that deacetylcinobufagin could be used as a preferred probe of SULT2A1. The regio-and stereo-selective sulfation properties of SULT2A1 and the structural variation effects of bufadienolides were investigated by docking analysis, which revealed the significance of appropriate molecule orientation and hydrophobic interactions of motifs with SULT2A1 His99 residues. Additionally, significant differences between humans and animal species were observed in the sulfation of bufalin and resibufogenin. This study provided important data for elucidating the mechanisms of bufadienolide sulfation and leads to a better understanding of the bufadienolide-SULT interaction which can be further used in preclinical development and rational use of bufadienolides.
Language英语
WOS IDWOS:000368941700074
PublisherROYAL SOC CHEMISTRY
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/171341
Collection中国科学院大连化学物理研究所
Corresponding AuthorMa, Xiaochi
Affiliation1.Dalian Med Univ, Acad Integrat Med, Coll Pharm, Dalian, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
3.Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
4.Peking Union Med Coll, Beijing 100021, Peoples R China
5.Dalian Med Univ, Coll Basic Med Sci, Dalian, Peoples R China
Recommended Citation
GB/T 7714
Ning, Jing,Cui, Yonglei,Wang, Chao,et al. Characterization of regio- and stereo-selective sulfation of bufadienolides: exploring the mechanism and providing insight into the structure-sulfation relationship by experimentation and molecular docking analysis[J]. RSC ADVANCES,2016,6(7):5774-5783.
APA Ning, Jing.,Cui, Yonglei.,Wang, Chao.,Dong, Peipei.,Ge, Guangbo.,...&Ma, Xiaochi.(2016).Characterization of regio- and stereo-selective sulfation of bufadienolides: exploring the mechanism and providing insight into the structure-sulfation relationship by experimentation and molecular docking analysis.RSC ADVANCES,6(7),5774-5783.
MLA Ning, Jing,et al."Characterization of regio- and stereo-selective sulfation of bufadienolides: exploring the mechanism and providing insight into the structure-sulfation relationship by experimentation and molecular docking analysis".RSC ADVANCES 6.7(2016):5774-5783.
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