Doctor of Philosophy, The Ohio State University, 2020, Pharmaceutical Sciences

Cancer remains the second-leading cause of death and more than 1.5 million people cancer will be diagnosed with this disease in the U.S. alone in 2020, with the mortality rate projected to be above 9 million worldwide. The availability of cancer treatments is still somewhat limited and many are expensive. Therefore, more affordable treatments from sustainable resources need to be found and utilized. Compounds derived from natural sources have been major contributors to the area of cancer chemotherapy for decades. Secondary metabolites from terrestrial and marine organisms have afforded numerous purified compounds, both in their unmodified naturally occurring forms and as semi-synthetic derivatives. Such compounds have been obtained primarily from terrestrial microbes and higher plants, with some found in marine animals. The presently available natural product oncology agents exhibit a variety of cellular mechanisms of action. As part of an ongoing effort to discover anticancer drug leads from tropical plants, a large-scale collection of Glycosmis ovoidea Pierre (Rutaceae) was made at Nui Chua National Park, Dahang Village, Vietnam. This taxonomically authenticated plant material was collected by abiding to the stipulations of currently accepted international conventions. Activity-guided fractionation of the chloroform-soluble fractions led to the isolation of compounds representing two different structural classes, a flavonoid and several coumarins. The new compound 1-(7-methoxy-2-oxo-2H-chromen-8-yl)-3-methyl-1-oxobut-2-en-2-yl (S)-2-methylbutanoate (147) was characterized structurally, and is a prenylated coumarin ester. This was isolated along with nine other compounds that were previously known, namely, murracarpin (141), 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (142), 7-hydroxycoumarin (143), murrayone (144), murralongin (145), kimcuongin (146), murragatin (148), minumicrolin (149), and minutuminolate (150). In order to confirm its structure and configura (open full item for complete abstract)

Committee: A. Douglas Kinghorn Ph.D., D.Sc. (Advisor); Karl Werbovetz Ph.D. (Committee Member); Pui-Kai Li Ph.D. (Committee Member) Subjects: Pharmacy Sciences; Philosophy of Science