title: Cytotoxic, cytostatic and HIV-1 PR inhibitory activities of the soft coral Litophyton arboreum.
abstract: Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide (4), alismoxide (5), (S)-chimyl alcohol (6), 7β-acetoxy-24-methylcholesta-5-24(28)-diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and 24-methylcholesta-5,24 (28)-diene-3β,7β,19-triol (9). Some of the isolated compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR). Compound 7 was strongly cytotoxic against HeLa cells (CC₅₀ 4.3 ± 0.75 µM), with selectivity index of SI 8.1, which was confirmed by real time cell electronic sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against HIV-1 PR at IC₅₀s of 7.20 ± 0.7, 4.85 ± 0.18, and 4.80 ± 0.92 µM respectively. In silico docking of most compounds presented comparable scores to that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8 showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic action in HeLa cells, revealing potential use in virostatic cocktails. Taken together, data presented here suggest Litophyton arboreum to contain promising compounds for further investigation against the diseases mentioned.
authors: Mona S
authors: MS
authors: Ellithey
authors: Namrita
authors: N
authors: Lall
authors: Ahmed A
authors: AA
authors: Hussein
authors: Department of Biochemistry, University of Pretoria, Pretoria 0002, South Africa. Debra.Meyer@up.ac.za.
authors: Debra
authors: D
authors: Meyer
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry* / Q000378:metabolism; D001685:Biological Factors / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000737:chemistry* / Q000494:pharmacology*; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020298:U937 Cells
chemical_list: D001685:Biological Factors; D054697:Cytostatic Agents; D003603:Cytotoxins; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1