文献类型：期刊文献

英文题名：Molecular Structure-Affinity Relationship of Bufadienolides and Human Serum Albumin In Vitro and Molecular Docking Analysis

作者：Zhou, Jing[1];Lu, Guodi[1,3];Wang, Honglan[1];Zhang, Junfeng[2];Duan, Jinao[1];Ma, Hongyue[1];Wu, Qinan[1]

第一作者：Zhou, Jing

通信作者：Ma, HY[1]

机构：[1]Nanjing Univ Chinese Med, Coll Pharm, Collaborat Innovat Ctr Chinese Med Resources Ind, Nanjing, Jiangsu, Peoples R China;[2]Nanjing Univ Chinese Med, Coll Basic Med, Nanjing, Jiangsu, Peoples R China;[3]Gansu Univ Tradit Chinese Med, Lanzhou, Peoples R China

第一机构：Nanjing Univ Chinese Med, Coll Pharm, Collaborat Innovat Ctr Chinese Med Resources Ind, Nanjing, Jiangsu, Peoples R China

通信机构：[1]corresponding author), Nanjing Univ Chinese Med, Coll Pharm, Collaborat Innovat Ctr Chinese Med Resources Ind, Nanjing, Jiangsu, Peoples R China.

年份：2015

卷号：10

期号：5

外文期刊名：PLOS ONE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000354049700139)】；

基金：National Science Fund (81102762, 30901894 and 81274199) http://www.nsfc.gov.cn/; Open Fund of Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXM-1-14) http://zyzyxt2011.njutcm.edu.cn; Six talent peaks project in Jiangsu Province (YY-015); A project founded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

摘要：The development of bufadienolides as anti-tumor agents is limited due to poor pharmacokinetic properties regarding drug half-lives and toxicity in vivo. These serious factors might be improved by increasing the drug/albumin-binding ratio. This study therefore investigated the relationship between the structural properties of nine bufadienolides and their affinities for human serum albumin (HSA) by a fluorescence spectroscopy-based analysis and molecular docking. Fluorescence quenching data showed that the interaction of each bufadienolide with HSA formed a non-fluorescent complex, while thermodynamic parameters revealed negative.S and.H values, corresponding to changes in enthalpy and entropy, respectively. The structural differences between the various bufadienolides markedly influenced their binding affinity for HSA. With the exception of a C = O bond at the C12 position that decreased the binding affinity for HSA, other polar groups tended to increase the affinity, especially a hydroxyl (OH) group at assorted bufadienolide sites. The rank order of binding affinities for drugs with tri-hydroxyl groups was as follows: 11-OH > 5-OH > 16-OH; in addition, 16-acetoxy (OAc), 10-aldehyde and 14-epoxy constituents notably enhanced the binding affinity. Among these groups, 11-OH and 16-acetyl were especially important for a seamless interaction between the bufadienolides and HSA. Furthermore, molecular docking analysis revealed that either an 11-OH or a 16-OAc group spatially close to a five-membered lactone ring significantly facilitated the anchoring of these compounds within site I of the HSA pocket via hydrogen bonding (H-bonding) with Tyr150 or Lys199, respectively. In summary, bufadienolide structure strongly affects binding with HSA, and 11-OH or 16-OAc groups improve the drug association with key amino acid residues. This information is valuable for the prospective development of bufadienolides with improved pharmacological profiles as novel anti-tumor drugs.