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.
Highlights
Natural products and their derivatives contribute more than half of all clinically administered drugs [1].Less than 1% of the isolated marine-derived natural products have been screened for their bioactivities [2].Many marine invertebrates such as sponges and ascidians are sessile and use highly evolved chemical compounds to attract food, block the growth of intruding neighbors or repel predators
The search for the bioactive compounds from marine ascidians is relatively young, but it is worthwhile mentioning that didemnin B, an ascidian metabolite, was the first marine natural product to be evaluated in a human clinical trial [4]
We describe the isolation, structure determination, and biological activities of two didemnaketal congeners, didemnaketal F (1) and G (2) (Figure 1) from a new collection of the Red Sea Didemnum species
Summary
Natural products and their derivatives contribute more than half of all clinically administered drugs [1]. Less than 1% of the isolated marine-derived natural products have been screened for their bioactivities [2] Many marine invertebrates such as sponges and ascidians (tunicates) are sessile (attached to the ocean floor) and use highly evolved chemical compounds to attract food, block the growth of intruding neighbors or repel predators. Didemnum is well-known for its diverse and bioactive secondary metabolites including cyclic peptides [6,7], alkaloids [8,9,10,11,12], macrolides [13,14,15], and N,N′-diphenethylurea [16] These metabolites were found to possess different biological activities such as antiplasmodial [17], antiviral [18,19], cytotoxic [20], and protein kinase inhibitors [13,14,15]. As reported before in didemnaketal E (Figure 1) [13], both 1 and possess a spiroketal/hemiketal functionality at the right part of the molecule
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