New Bioactive Compounds From A Marine Sponge Spongosorites Sp.

Marine natural products are becoming a promising resort for finding many leads with a variety of novel scaffolds. Target-based high throughout screening of bioactive marine natural products will give totally innovated drugs, which were never encountered in terrestrial systems. Among marine organisms, sponges appear to be one of the richest phylum in bioactive species. Indole alkaloids, especially bisindole alkaloids are widely recognized as one of the growing groups of marine sponge metabolites. Some of these metabolites exhibit potent and diverse bioactivities such as cytotoxicity, antitumor, antiviral, antifungal, and anti-inflammatory. In our search for bioactivite metabolites from a marine sponge Spongosorites sp., collected from Korean waters, twenty-four bisindole alkaloids and six monoindole alkaloids have been isolated from the brine shrimp active fraction of the MeOH extract.The gross structure of the compounds were elucidated as five new (1-3, 6, 7) and three known (4, 5, 8) hamacanthins, one new (9) and six known (10-15) dihydrohamacanthins, one new (16) and five known (17-21) topsentins, three new 4, 5-dihydrotopsentins (spongotines) (22-24), two new (25, 26) indol-oxoacetic acid methyl esters, two new (27, 28) indol-oxoacetamides, one new (29) and one known (30) indol-formic acid methyl ester. Compounds 25-28 were unique indole derivatives with 1,2-diketone functionality. Co-occurring bisindoles might be biosynthesized by condensation of two units of these compounds. It is noteworthy that both R and S isomers were isolated for the hamacanthins (1-8), while a single stereoisomer was isolated for dihydrohamacanthins (9-15). The planar structures were established on the basis of COSY, HMBC, and HSQC NMR and MS spectroscopic analyses. Configurations of these compounds were derived from ~1H-~1H coupling constants, ROESY NMR spectroscopy and optical rotation. A series of new type of compounds, 4,5-dihydrotopsentins that were previous erroneously reported, have been isolated and given a a trivial name spongotines. The strong evidence was provided in case to clearly distinguish the confusing hamacanthin class of compounds from the topsentin class of compound for the first time.Compounds 1-30 were further tested for cytotoxicity against five human solid cancer cell lines [employed cell lines were A549, human lung cancer; SK-OV-3, human ovarian cancer; SK-MEL-2, human skin cancer; XF498, human CNS cancer; and HCT15, human colon cancer]. Compounds 1, 3-15, 18, 21, 22, 24 and 30 showed moderate to marginal cytotoxicity against five human tumor cell lines. Among them, compounds 1, 4, 5, 7, 8, 10, 12, 14, 22, and 24 showed moderate to marginal cytotoxicity against all the five human tumor cell lines, while compounds 3, 6, 9, 11, 13, 15, 18, 21, and 30 showed somewhat selective cytotoxicity against some of the five cell lines.Compounds 1-3, 5, 6, 10-14, and 23 were also assayed for antibacterial activity against 20 clinically isolated methicillin-resistant strains. Compounds 2, 5, 12, and 14 showed weak antibacterial activity against Streptococcus pyogenes 308A, Streptococcus pyogenes 77A, Streptococcus aureus SG 511, Streptococcus aureus 285, Streptococcus aureus 503, Pseudomonas aeruginosa 1771, and Klebsiella oxytoca 1082 E.