title: Identification of compounds with cytotoxic activity from the leaf of the Nigerian medicinal plant, Anacardium occidentale L. (Anacardiaceae).
abstract: Cancer is now the second-leading cause of mortality and morbidity, behind only heart disease, necessitating urgent development of (chemo)therapeutic interventions to stem the growing burden of cancer cases and cancer death. Plants represent a credible source of promising drug leads in this regard, with a long history of proven use in the indigenous treatment of cancer. This study therefore investigated Anacardium occidentale, one of the plants in a Nigerian Traditional Medicine formulation commonly used to manage cancerous diseases, for cytotoxic activity. Bioassay-guided fractionation, spectroscopy, Alamar blue fluorescence-based viability assay in cultured HeLa cells and microscopy were used. Four compounds, zoapatanolide A (1), agathisflavone (2), 1,2-bis(2,6-dimethoxy-4-methoxycarbonylphenyl)ethane (anacardicin, 3) and methyl gallate (4), were isolated, with the most potent being zoapatanolide A with an IC50value of 36.2±9.8µM in the viability assay. To gain an insight into the likely molecular basis of their observed cytotoxic effects, Autodock Vina binding free energies of each of the isolated compounds with seven molecular targets implicated in cancer development (MAPK8, MAPK10, MAP3K12, MAPK3, MAPK1, MAPK7 and VEGF), were calculated. Pearson correlation coefficients were obtained with experimentally-determined IC50in the Alamar blue viability assay. While these compounds were not as potent as a standard anticancer compound, doxorubicin, the results provide reasonable evidence that the plant species contains compounds with cytotoxic activity. This study provides some evidence of why this plant is used ethnobotanically in anticancer herbal formulations and justifies investigating Nigerian medicinal plants highlighted in recent ethnobotanical surveys.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile Ife, Nigeria; School of Pharmacy, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, England, United Kingdom. Electronic address: bamit@oauife.edu.ng.
authors.forename: Bamigboye J
authors.initials: BJ
authors.lastname: Taiwo
authors.affiliation: School of Pharmacy, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, England, United Kingdom. Electronic address: A.A.Fatokun@ljmu.ac.uk.
authors.forename: Amos A
authors.initials: AA
authors.lastname: Fatokun
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile Ife, Nigeria.
authors.forename: Olujide O
authors.initials: OO
authors.lastname: Olubiyi
authors.affiliation: Department of Physiology, Faculty of Basic Medical Science, Obafemi Awolowo University, Ile Ife, Nigeria; Department of Paediatrics, Federal Teaching Hospital, Ido-Ekiti, Ekiti State, Nigeria.
authors.forename: Olukemi T
authors.initials: OT
authors.lastname: Bamigboye-Taiwo
authors.affiliation: School of Chemistry and Physics, Pietermaritzburg Campus, University of KwaZulu-Natal, Private Bag X01, Scottsville 3209, South Africa.
authors.forename: Fanie R
authors.initials: FR
authors.lastname: van Heerden
authors.affiliation: School of Pharmacy, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, England, United Kingdom.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Wright
mesh_terms: D027926:Anacardiaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009549:Nigeria; D018515:Plant Leaves / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic
keywords: Cancer; Cytotoxicity; Drug discovery; Lead compound; Nigerian medicinal plants