BIOASSAY GUIDED FRACTIONATION AS A TOOL FOR CORRELATING CYTOTOXICITY AND PHYTOTOXICITY

Abstract

A characteristic feature of plants is the ability to synthesize a wide range of secondary metabolites. The question arises as to why plants invest so much energy and care in the formation of these compounds. The main function appears to be chemical defense against microorganisms, herbivores, and other competing plant species (allelopathy). However, these metabolites may have more than one function or biological activity. For example, compounds may be an attractant for insects and be antibiotic and UV-protectant at the same time. Reported biological activities of secondary metabolites include antimicrobial, antifungal, cytotoxicity, and phytotoxicity. Although some secondary metabolites have been reported to have activity in more than one biological system, researchers tend to focus on one area of study and therefore may not document other biological activities outside their focus. One area which has not been extensively explored is the possible correlation between phytotoxicity and cytotoxicity. This study was designed to explore, through bioassay guided fractionation, whether such a correlation exists. The fractionation and isolation of secondary metabolites was bioassay-guided using the aquatic plant, Lemna minor, to test for plant phytotoxicity. Fractions were simultaneously submitted to the National Cancer Institute's 60-cell line human tumor screen to test for cytotoxicity. Using this method, three compounds were isolated from a marine gorgonian. Buddledin C and buddledin D have previously been isolated from a terrestrial plant and reported to show piscicidal activity. Suberosenone is a novel compound which has a rare tricyclic quadrone-type carbon skeleton. It shows antitumor activity with a mean GI50of 0.06 μM in the NCI's antitumor screen. Suberosenone also has phytotoxic activity with a mean G150of 46 μWI in the Lemna minor bioassay. Suberosenone is the first representative of the quadrone class of sesquiterpenes isolated from a marine organism.