| An ideal chemotherapeutic agent is far from being discovered, as cancer remains the second leading cause of deaths in the United States. The marine environment represents a complex and untapped resource for the discovery of novel anticancer leads. Marine invertebrates like soft corals are known to produce exceptionally large amounts of terpenoid metabolites possessing wide range of bioactivities. Particularly, sarcophytol A, which is a cembranoid isolated from the soft coral Sarcophyton glaucum of Okinawan origin, is currently under clinical investigation for its chemopreventive activity.;Sarcophine, a structurally related cembranoid, was first isolated from the same coral species found in the Red Sea. The yield of this compound was up to 4% of the animal's dry weight. Sarcophine is known to possess moderate anticancer potential that is enhanced through biocatalytic and semisynthetic transformations. Further, in addition to Sarcophine, the Red Sea soft coral is known to be a source of several other terpenoids, which remain uninvestigated for their anticancer potential. Hence, we hypothesized that the cembranoids and sesquiterpenes from the Red Sea soft coral S. glaucum might possess anticancer properties that could be further optimized. Accordingly, the specific aims of this study were to extract, isolate, and characterize terpenes from S. glaucum, to derivatize the major terpenoids, including Sarcophine, with the aid of biocatalysis and/or semisynthesis, and to evaluate the anticancer potential of the resulting natural, biocatalytic, and semisynthesic terpenes.;A novel sesquiterpene, dioxasarcoguaiacol was isolated in addition to several other terpenes. (+)-Alloaromadendrene was the most potent compound, inhibiting the malignant +SA mammary epithelial cell proliferation at a dose of 20 muM. Sarcophine and 2-epi-16-deoxysarcophine were isolated in reasonable yields for derivatization. Semisynthetic and biocatalytic transformations of sarcophine and 2-epi-16-deoxysarcophine generated structurally diverse derivatives with enhanced activities. The antimetastatic properties of the cembranoids were demonstrated for the first time using wound healing assays. The structure elucidation of these compounds was mainly based on extensive nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), and, in some cases, molecular modeling studies. These studies demonstrated that the cembranoids and guaiane sesquiterpenes from the Red Sea soft coral Sarcophyton glaucum are potential anticancer leads. |
