Phytochemical and Chemotaxonomic Investigations on Ferula szowitsiana DC. and Allied Taxa of the Genus Ferula from Anatolia, Turkey

Abstract

Phytochemical and Chemotaxonomic Investigations on Ferula szowitsiana DC. and Allied Taxa of the Genus Ferula from Anatolia, Turkey Fatma Memnune Erucar1,2 , Sarath P. D. Senadeera 1 , Ph.D., John A. Beutler, Ph.D.1 , Mahmut Miski, Ph.D.2 1. National Institutes of Health, National Cancer Institute, Molecular Targets Program, Frederick, MD 2. Istanbul University, Faculty of Pharmacy, Department of Pharmacognosy, Istanbul, Turkey Currently, cancer is the second-leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Due to differences in genetic factors among people, the disease requires various treatment options that have numerous and complicated stages during the aggressive transformation from normal cells to tumor cells. Moreover, because of resistant and mutant cancer cells, some of the effective drugs may not work overtime, thus making it one of the most challenging diseases to cure. Ferula is a genus with approximately 185 species widely distributed in Asian and Mediterranean countries. Oleo-gum-resins and roots of various Ferula species have been used for the treatment of cancer for thousands of years in Turkey and chemical constituents isolated from the species of Ferula have exhibited high cytotoxic activity. Thus, new cytotoxic molecules that are isolated or derived from Ferula species may have a potential in the elucidation of the pharmacophore groups of cancer drugs. We carried out research on Ferula szowitsiana DC collected from Turkey to isolate cytotoxic compounds through bioactivity-directed isolation. Initially, methanol and dichloromethane extracts of the root of Ferula szowitsiana was screened against colon cancer cell lines (COLO205, KM12) with the dichloromethane extract being active. Therefore, the dichloromethane extract was fractionated on Sephadex LH-20 with hexane-dichloromethane-methanol (7:4.5:0.5) to obtain 42 fractions and these fractions were re-tested against colon (COLO205, HCT116) and renal (A498, UO31) cell lines. Six fractions were found active and they were further fractionated using reverse phase HPLC to isolate the pure compounds badrakemin, conferol, colladonin, gummosin, kellerin, and a new compound. These compounds were tested for their cytotoxic activity. Structures of the isolated compounds were determined from analysis of 1D and 2D NMR spectroscopy and mass spectrometry.