Methoxy‐flavones Identified from Ageratum conyzoides Induce Caspase ‐3 and ‐7 Activations in Jurkat Cells

Abstract

New therapies for leukemia are urgently needed due to adverse side effects, tumor resistance and lack of selectivity of many chemotherapeutic agents in clinical use. Ageratum conyzoides has been used in folklore medicine for managing leukemia and other cancers. Thus, this study aimed to investigate the effects of fractions, sub-fractions and purified compounds from the ethanol leaf extracts of A. conyzoides against Jurkat cells-model for acute T cell leukemia. A two-dimensional purification process using normal phase flash, followed by reverse phase purification was necessary to isolate pure methoxy-flavones, which were further characterized by Nuclear Magnetic Resonance (NMR) and MS-MS. The effect of fractions or pure compounds on cell viability was determined using either the MTT reagent or CellTiter-Blue® assay, while the caspase-3 and -7 activation was tested with Caspase-Glo® 3/7 assay. Prediction of compounds' drug disposition profiles in vivo was measured with biomimetic affinity chromatography methodologies. The most promising compounds were identified as 5, 6, 7, 3’, 4’, 5’- and 5, 6, 7, 8, 3’, 4’-hexamethoxyflavones and were found to induce caspase -3 and -7 activities, which correlated to their reduced cell viability. The physicochemical profiles predict on-target actions with fewer propensities for off-target promiscuity due to a low CHI IAM7.4 affinity to phospholipid. The results obtained in this study give an initial scientific insight on the usefulness of traditionally used A. conyzoides and provides a basis for further investigation of the active components which could be useful in the development of new leukemic therapies. Support or Funding Information Novartis Institutes for Bio-Medical Research Incoporation, Cambridge, MA 02139, USA. Department of Biochemistry and Biotechnology, KNUST, Kumasi-Ghana. Noguchi Memorial Institute of Medical Research, UG, Accra-Ghana. Structures of isolated compounds: 5, 6, 7, 3’, 4’, 5’-hexamethoxyflavone (1); 5, 6, 7, 8, 3’, 4’-hexamethoxyflavone (2); 5, 6, 7, 8, 3’, 4’, 5’-heptamethoxyflavone (3); 5, 6, 7, 3’, 4’-pentamethoxyflavone (4); 5,6, 7, 3'-tetramethoxy-4', 5'-methylenedioxyflavone (5). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.