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.
Highlights
HIV/AIDS is one of the most devastating diseases in the world with approximately 34 million people living with the virus in 2010 and approximately 2.7 million new infections in that same year [1]
HIV protease inhibitors were developed in the early 1990s, and their subsequent incorporation into highly active antiretroviral therapy (HAART) has profoundly changed the natural history of HIV
In the 3D stereo-diagram of acetyl pepstatin bound to the HIV-1 protease active site shown in Figure 8, the X-ray structure clearly reveals that most of the amino acid moieties surrounding the inhibitor are hydrophobic
Summary
HIV/AIDS is one of the most devastating diseases in the world with approximately 34 million people living with the virus in 2010 and approximately 2.7 million new infections in that same year [1]. Antiretroviral therapy (ART) successfully reduces infection and decreases symptoms; but, the emergence of viral drug resistance, due to drug-induced mutations in viral genes, renders treatment ineffective This underscores an urgent need to develop new anti-HIV drugs [2,3] with fewer side-effects to improve patient compliance. Parts of the Red Sea showed the presence of cembranoide diterpenes [7], which had moderate cytotoxicity in HeLa cells Collections of this soft coral from other parts of the world showed different metabolites of this soft coral, e.g., furanocembranoides, which demonstrated antiproliferative activities against the cell lines L-929 and K-562 [8], sesquiterpenes, sterols, and fatty acid derivatives [9,10] all believed to contain medicinal properties. The anti-HIV and anti-cancer potential of some of the purified compounds from the soft coral is reported here for the first time
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