title: Didemnaketals f and g, new bioactive spiroketals from a red sea ascidian didemnum species.
abstract: In continuation of our ongoing efforts to identify bioactive compounds from Red Sea marine organisms, a new collection of the ascidian Didemnum species was investigated. Chromatographic fractionation and HPLC purification of the CH2Cl2 fraction of an organic extract of the ascidian resulted in the identification of two new spiroketals, didemnaketals F (1) and G (2). The structure determination of the compounds was completed by extensive study of 1D (1H, 13C, and DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments in addition to high-resolution mass spectral data. Didemnaketal F (1) and G (2) differ from the previously reported compounds of this class by the lack the terminal methyl ester at C-1 and the methyl functionality at C-2. Instead, 1 and 2 possess a methyl ketone moiety instead of the terminal ester. Furthermore, didemnaketal F possesses a disubstituted double bond between C-2 and C-3, while the double bond was replaced by a secondary alcohol at C-3 in didemnaketal G. In addition, they possess the unique spiroketal/hemiketal functionality which was previously reported in didemnaketal E. Didemnaketals F (1) and G (2) displayed moderate activity against HeLa cells with of IC50s of 49.9 and 14.0 µM, respectively. In addition, didemnaketal F (1) displayed potent antimicrobial activity against E. coli and C. albicans. These findings provide further insight into the biosynthetic capabilities of this ascidian and the chemical diversity as well as the biological activity of this class of compounds.
authors.affiliation: Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. lshalla@kau.edu.sa.
authors.forename: Lamiaa A
authors.initials: LA
authors.lastname: Shaala
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. dyoussef@kau.edu.sa.
authors.forename: Diaa T A
authors.initials: DT
authors.lastname: Youssef
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. sabrinshaur@gmail.com.
authors.forename: Sabrin R M
authors.initials: SR
authors.lastname: Ibrahim
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. gamals2001@yahoo.com.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Mohamed
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. jihanbadr2010@hotmail.com.
authors.forename: Jihan M
authors.initials: JM
authors.lastname: Badr
authors.affiliation: Department of Pharmacology and Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. risingera@uthscsa.edu.
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.affiliation: Department of Pharmacology and Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. mooberry@uthscsa.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents; D002176:Candida albicans / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D019156:Indian Ocean; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014561:Urochordata / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D005663:Furans; D013141:Spiro Compounds; C000599725:didemnaketal F; C000599726:didemnaketal G; C520774:spiroketal