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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MDPI AG
2025-06-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/7/262 |
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| author | Lamiaa A. Shaala Diaa T. A. Youssef Hadeel Almagthali Ameen M. Almohammadi Wafaa T. Arab Torki Alzughaibi Noor M. Bataweel Reham S. Ibrahim |
| author_facet | Lamiaa A. Shaala Diaa T. A. Youssef Hadeel Almagthali Ameen M. Almohammadi Wafaa T. Arab Torki Alzughaibi Noor M. Bataweel Reham S. Ibrahim |
| author_sort | Lamiaa A. Shaala |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-37ea304b88b544f0ba27268362be2df2 |
| institution | DOAJ |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| spelling | doaj-art-37ea304b88b544f0ba27268362be2df22025-08-20T02:47:19ZengMDPI AGMarine Drugs1660-33972025-06-0123726210.3390/md23070262Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> SpeciesLamiaa A. Shaala0Diaa T. A. Youssef1Hadeel Almagthali2Ameen M. Almohammadi3Wafaa T. Arab4Torki Alzughaibi5Noor M. Bataweel6Reham S. Ibrahim7Suez Canal University Hospitals, Suez Canal University, Ismailia 41522, EgyptDepartment of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Taif University, Al-Haweiah 21974, Saudi ArabiaDepartment of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaVaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi ArabiaKing Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptMarine 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.https://www.mdpi.com/1660-3397/23/7/262Red Sea tunicate<i>Didemnum</i> speciesbioactive compoundsdidemnosides A and Bhuman cancer cell linesantiproliferative activity |
| spellingShingle | Lamiaa A. Shaala Diaa T. A. Youssef Hadeel Almagthali Ameen M. Almohammadi Wafaa T. Arab Torki Alzughaibi Noor M. Bataweel Reham S. Ibrahim Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species Marine Drugs Red Sea tunicate <i>Didemnum</i> species bioactive compounds didemnosides A and B human cancer cell lines antiproliferative activity |
| title | Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species |
| title_full | Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species |
| title_fullStr | Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species |
| title_full_unstemmed | Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species |
| title_short | Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species |
| title_sort | didemnosides a and b antiproliferative nucleosides from the red sea marine tunicate i didemnum i species |
| topic | Red Sea tunicate <i>Didemnum</i> species bioactive compounds didemnosides A and B human cancer cell lines antiproliferative activity |
| url | https://www.mdpi.com/1660-3397/23/7/262 |
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