Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei.
In our search for bioactive metabolites from marine organisms, we have investigated the polar fraction of the organic extract of the Red Sea sponge Theonella swinhoei. Successive chromatographic separations and final HPLC purification of the potent antifungal fraction afforded a new bicyclic glycopeptide, theonellamide G. The structure of the peptide was determined using extensive 1D and 2D NMR and high-resolution mass spectral determinations. The absolute configuration of theonellamide G was determined by chemical degradation and 2D NMR spectroscopy. Theonellamide G showed potent antifungal activity towards wild and amphotericin B-resistant strains of Candida albicans with IC₅₀ of 4.49 and 2.0 μM, respectively. Additionally, it displayed cytotoxic activity against the human colon adenocarcinoma cell line (HCT-16) with IC₅₀ of 6.0 μM. These findings provide further insight into the chemical diversity and biological activities of this class of compounds.
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. dyoussef@kau.edu.sa.
Diaa T A
DT
Youssef
Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. lshalla@kau.edu.sa.
Lamiaa A
LA
Shaala
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. gahussein@kau.edu.sa.
Gamal A
GA
Mohamed
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. jibrahim@kau.edu.sa.
Jihan M
JM
Badr
Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. fbamanea@kau.edu.sa.
Faida H
FH
Bamanie
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. sribrahim@taibahu.edu.sa.
Sabrin R M
SR
Ibrahim
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D006020:Glycopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D019156:Indian Ocean; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D047232:Theonella / Q000737:chemistry*
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D006020:Glycopeptides; D010456:Peptides, Cyclic; C000593335:theonellamide G