Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species

Marine tunicates are a very attractive and abundant source of secondary metabolites with chemical diversity and biological activity. Fractionation and purification of the organic extract of the Red Sea tunicate <i>Didemnum</i> species resulted in the isolation and identification of three...

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Main Authors: Lamiaa A. Shaala, Diaa T. A. Youssef, Hadeel Almagthali, Ameen M. Almohammadi, Wafaa T. Arab, Torki Alzughaibi, Noor M. Bataweel, Reham S. Ibrahim
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/23/7/262
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Summary:Marine tunicates are a very attractive and abundant source of secondary metabolites with chemical diversity and biological activity. Fractionation and purification of the organic extract of the Red Sea tunicate <i>Didemnum</i> species resulted in the isolation and identification of three new compounds, didemnosides A and B (<b>1</b> and <b>2</b>) and 1,1′,3,3′-bisuracil (<b>3</b>), together with thymidine (<b>4</b>), 2′-deoxyuridine (<b>5</b>), homarine (<b>6</b>), and acetamide (<b>7</b>). Planar structures of the compounds were explained through analyses of their 1D (<sup>1</sup>H and <sup>13</sup>C) and 2D (<sup>1</sup>H–<sup>1</sup>H COSY, HSQC, and HMBC) NMR spectra and high-resolution mass spectral determinations. Compound <b>1</b> exhibited the highest growth inhibition toward the MCF-7 cancer cell line with IC<sub>50</sub> values of 0.597 μM, while other compounds were inactive (≥50 μM) against this cell line. On the other hand, compounds <b>1</b>, <b>2</b>, and <b>4</b>–<b>7</b> moderately inhibited SW-1222 and PC-3 cells with IC<sub>50</sub> values ranging between 5.25 and 9.36 μM. Molecular docking analyses of the top three active compounds on each tested cell line exposed stable interactions into the active pockets of estrogen receptor alpha (ESR1), human topoisomerase II alpha (TOP2A), and cyclin-dependent kinase 5 (CDK5) which are contemplated as essential targets in cancer treatments. Thus, compound <b>1</b> represents a scaffold for the development of more effective anticancer drugs.
ISSN:1660-3397