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从被囊动物(吉布提穆查岛海域)中提取的层状生物碱衍生物的抗癌特性评估:药理学和计算方法

Evaluation of the Anticancer Properties of Lamellar Alkaloid Drivatives Extracted from the Tunicate (Moucha Island Sea, Djibouti): Pharmacological and Computational Approach.

作者信息

Abdoul-Latif Fatouma Mohamed, Aboubaker Ibrahim Houmed, Mohamed Houda, Ainane Ayoub, Chakrouni Mouhcine, Ali Ali Merito, Jutur Pannaga Pavan, Ainane Tarik

机构信息

Medicinal Research Institute, Center for Research and Study of Djibouti, BP 486, Djibouti City P.O. Box 486, Djibouti.

Peltier Hospital of Djibouti, Djibouti City P.O. Box 2123, Djibouti.

出版信息

Molecules. 2025 Aug 11;30(16):3338. doi: 10.3390/molecules30163338.

Abstract

This study aimed to evaluate the anticancer activity of lamellar alkaloid derivatives extracted from the tunicate from Moucha Island (Djibouti), focusing on their antiviability against human cell lines and using biocomputational analyses via the Integrated Biomolecular Profiling and Mechanism Evaluation (IBProME) method to understand their mechanisms of action. Two alkaloids were isolated, lamellarin D and lamellarin T, whose structures were confirmed by state-of-the-art analytical techniques. Cell viability tests were performed on PC3, A549 and JIMT-T1 cell lines, and IBProME analyses were used to predict their interactions with p53 protein and evaluate their toxicological and pharmacokinetic profiles. The results showed that lamellarin D was particularly effective against prostate and lung cancer cells, with respective IC values of 5.25 µg/mL and 8.64 µg/mL, close to those of doxorubicin. In contrast, lamellarin T showed less marked activity but remains promising. Computational analyses via IBProME highlighted differences in chemical reactivity between the two compounds, with lamellarin D being more reactive. Toxicity tests revealed that lamellarin D exhibited lower acute toxicity than lamellarin T. In terms of pharmacokinetic properties, both molecules showed low absorption and moderate bioavailability, although lamellarin T displayed more marked lipophilicity. These results suggest that lamellars, particularly lamellarin D, have therapeutic potential for the treatment of certain types of cancer.

摘要

本研究旨在评估从吉布提穆查岛被囊动物中提取的层状生物碱衍生物的抗癌活性,重点关注其对人类细胞系的抗生存能力,并通过综合生物分子谱分析和作用机制评估(IBProME)方法进行生物计算分析,以了解其作用机制。分离出了两种生物碱,即片螺素D和片螺素T,其结构通过先进的分析技术得以确认。对PC3、A549和JIMT-T1细胞系进行了细胞生存能力测试,并使用IBProME分析来预测它们与p53蛋白的相互作用,以及评估它们的毒理学和药代动力学特征。结果表明,片螺素D对前列腺癌和肺癌细胞特别有效,其IC值分别为5.25微克/毫升和8.64微克/毫升,接近阿霉素的值。相比之下,片螺素T的活性不太明显,但仍有前景。通过IBProME进行的计算分析突出了这两种化合物之间化学反应性的差异,片螺素D的反应性更强。毒性测试表明,片螺素D的急性毒性低于片螺素T。在药代动力学特性方面,尽管片螺素T表现出更明显的亲脂性,但这两种分子的吸收都较低,生物利用度适中。这些结果表明,层状生物碱,特别是片螺素D,对某些类型癌症的治疗具有潜在的治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc2/12388770/b08342ffb1dc/molecules-30-03338-g001.jpg

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