Identification of Bioactive Metabolites from Marine Invertebrates

Abstract

Natural products have been major source of drugs. 64% of all druggable new small molecules discovered from 1981 to 2010 were originated from natural organisms. Over 70% of the surface of the earth is covered with the ocean and over 80% of organisms inhabit the ocean. Specially, marine invertebrates such as sponges and tunicates produce secondary metabolites using chemical defence mechanisms to survive in severe marine environments. Discovery, isolation, biochemical/pharmacological characterization, pre-clinical and clinical trial of drugs derived from marine environment are continuously developing and increasing. One of the most promising areas is cancer therapy. It was established that 118 marine natural products (MNPs) are currently in pre-clinical trials, 22MNPs in clinical trials and 3 MNPs on the market. Marine sponge of the genus Phorbas are known to be rich sources of structurally unique and biologically active secondary metabolites. Since finding phorbazoles, novel metabolites have been continuously isolated from these animals. Bioactivity-guided fractionation followed by reversed-phase HPLC gave three new sesterterpenes. Thiers chemical structures were elucidated by interpretation of spectroscopic data and absolute stereochemistry also was determined by interpretation of CD and spectroscopic data. The cytotoxicity tests for Compounds A-C (1-3) were carried out against three human cancer cell lines using the colorimetric methylthiazole tetrazolium bromide (MTT). The compound A (1) showed moderate cytotoxicity against human pancreas cancer panc-1 with an IC50 = 11.4 μM, human renal cancer A498 with an IC50 = 18.7 μM, and human renal cancer ACHN with an IC50 = 24.4 μM.