title: Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer.
abstract: The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of -12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8-6.9 µM) in comparison to a reference standard Tamoxifen (18.9-24.1 µM) within the tested time point (24-72 h). The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules.
authors.affiliation: Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Malaysia. ettiimaobong@gmail.com.|Department of Pharmacology and Toxicology, University of Uyo, Uyo 520271, Nigeria. ettiimaobong@gmail.com.
authors.forename: Imaobong
authors.initials: I
authors.lastname: Etti
authors.affiliation: Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang 43400, Malaysia. rasedee@upm.edu.my.
authors.forename: Rasedee
authors.initials: R
authors.lastname: Abdullah
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. najihahmh@um.edu.my.
authors.forename: Najihah Mohd
authors.initials: NM
authors.lastname: Hashim
authors.affiliation: Department of Veterinary Preclinical Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Malaysia. arifah@vet.upm.edu.my.
authors.forename: Arifah
authors.initials: A
authors.lastname: Kadir
authors.affiliation: MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia. zer2crystals@gmail.com.
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.affiliation: Department of Agricultural and Food Engineering, University of Uyo, Uyo 520271, Nigeria. christopheretti@uniuyo.edu.ng.
authors.forename: Christopher
authors.initials: C
authors.lastname: Etti
authors.affiliation: MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia. keepibinformed@yahoo.co.uk.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Malami
authors.affiliation: MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia. petermwaziri@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Waziri
authors.affiliation: Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, University Putra Malaysia, Serdang 43400, Malaysia. cwhow2000@yahoo.com.
authors.forename: Chee Wun
authors.initials: CW
authors.lastname: How
mesh_terms: D000596:Amino Acids; D031622:Artocarpus / Q000737:chemistry; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000596:Amino Acids; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D008024:Ligands; D011960:Receptors, Estrogen; C066727:artonin E
keywords: Artocarpus; Artonin E; human estrogen receptor; in silico; molecular docking