Ren Yulin, Kaweesa Elizabeth N, Zhou Ruoheng, Liu Yue, Sydara Kongmany, Xayvue Mouachanh, Soejarto Djaja D, Wu Sijin, Cheng Xiaolin, Burdette Joanna E, Kinghorn A Douglas
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
J Nat Prod. 2025 Jan 24;88(1):183-190. doi: 10.1021/acs.jnatprod.4c01257. Epub 2025 Jan 14.
(-)-Cryptanoside A () was identified previously as a major cytotoxic component of the stems of collected in Laos, which mediates its activity by targeting Na/K-ATPase (NKA), with hydrogen bonds formed between its 11- and 4'-hydroxy groups and NKA being observed in its docking profile. In a continuing investigation, and its 17-epimer, (-)-17--cryptanoside A (), and the new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid () and the known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone () pregnane-type steroids were isolated from . In addition, (-)-11,4'-di--acetylcryptanoside A () has been synthesized from the acetylation of . The structures of these compounds were determined by analysis of their spectroscopic data, with their cytotoxic and NKA inhibitory activities being evaluated. In contrast to that exhibited potent activities, the other compounds were largely inactive. Molecular docking profiles indicated that - and bind to NKA, but some subtle differences were observed in their interactions with NKA, which may contribute to their differential cytotoxic and NKA inhibitory potency.
(-)-隐丹参苷A()先前被鉴定为采自老挝的[植物名称]茎中的主要细胞毒性成分,它通过靶向钠钾-ATP酶(NKA)介导其活性,在其对接图谱中观察到其11-羟基和4'-羟基与NKA之间形成了氢键。在一项持续的研究中,从[植物名称]中分离出了隐丹参苷A及其17-差向异构体(-)-17-表-隐丹参苷A(),以及新的(+)-2-羟基雄甾-4,6-二烯-3-酮-17-羧酸()和已知的(+)-2,21-二羟基孕甾-4,6-二烯-3,20-二酮或2-羟基-6,7-二脱氢皮质酮()孕烷型甾体。此外,(-)-11,4'-二-O-乙酰基隐丹参苷A()是通过[化合物名称]的乙酰化反应合成的。这些化合物的结构通过光谱数据分析确定,并对它们的细胞毒性和NKA抑制活性进行了评估。与表现出强效活性的隐丹参苷A相比,其他化合物大多无活性。分子对接图谱表明,隐丹参苷A和17-表-隐丹参苷A与NKA结合,但在它们与NKA的相互作用中观察到一些细微差异,这可能导致它们细胞毒性和NKA抑制效力的差异。