Cytotoxic and Noncytotoxic Steroidal Constituents of Cryptolepis dubia.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2025-01-14 DOI:10.1021/acs.jnatprod.4c01257

Yulin Ren, Elizabeth N Kaweesa, Ruoheng Zhou, Yue Liu, Kongmany Sydara, Mouachanh Xayvue, Djaja D Soejarto, Sijin Wu, Xiaolin Cheng, Joanna E Burdette, A Douglas Kinghorn

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引用次数: 0

Abstract

(-)-Cryptanoside A (1) was identified previously as a major cytotoxic component of the stems of Cryptolepis dubia 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, 1 and its 17-epimer, (-)-17-epi-cryptanoside A (2), and the new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid (3) and the known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone (4) pregnane-type steroids were isolated from C. dubia. In addition, (-)-11,4'-di-O-acetylcryptanoside A (1a) has been synthesized from the acetylation of 1. 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 1 that exhibited potent activities, the other compounds were largely inactive. Molecular docking profiles indicated that 1-3 and 1a 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.

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隐藻的细胞毒性和非细胞毒性甾体成分。

（-）- cryptanoside A(1)先前被鉴定为在老挝收集的Cryptolepis dubia茎中的主要细胞毒性成分，它通过靶向Na+/K+- atp酶（NKA）介导其活性，在其对接谱中观察到其11-和4'-羟基与NKA之间形成氢键。在一个持续的研究中，1及其17-外聚体，(-)-17-外隐皮苷a(2)，新的(+)-2-羟基雄androsta-4,6-二烯-3- 1- 17-羧酸(3)和已知的(+)-2,21-二羟基孕酮-4,6-二烯-3,20-二酮或2-羟基-6,7-二脱氢皮质酮(4)孕酮类类固醇从双鱼中分离出来。此外，由1的乙酰化合成了(-)-11,4'-二- o -乙酰隐皮苷A （1a）。通过光谱数据分析确定了这些化合物的结构，并评估了它们的细胞毒性和NKA抑制活性。与1表现出强大的活性相比，其他化合物基本上没有活性。分子对接图谱表明，1-3和1a与NKA结合，但在与NKA的相互作用中观察到一些微妙的差异，这可能是它们的细胞毒性和NKA抑制能力不同的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.