title: Molecular Docking Analysis of Steroid-based Copper Transporter 1 Inhibitors.
abstract: Copper transporter 1 (CTR1) represents an important determinant of cisplatin resistance. A series of 35 semi-substituted steroids were recently investigated on cisplatin-resistant CTR1-expressing A2780cis ovarian carcinoma cells as well as their parental sensitive counterparts regarding their cytotoxic and resistance-reversing features. In the present investigation, three compounds ( 4: , 5: , 25: ) were selected for molecular docking analysis on the homology-modelled human CTR1 transmembrane domain. Steroids 4: , 5: and 25: interacted with CTR1 at a similar docking pose and with even higher binding affinities than the known CTR1 inhibitor, cimetidine. Applying the defined docking mode, the binding energies were found to be -7.15±<0.001 kcal/mol (compound 4: ), -8.71±0.06 kcal/mol (compound 5: ), -7.63±0.01 kcal/mol (compound 25: ), and -5.05±0.02 kcal/mol (for cimetidine). These steroids have the potential for further development as CTR1 inhibitors overcoming cisplatin resistance.
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Onat
authors.initials: O
authors.lastname: Kadioglu
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Julianna
authors.initials: J
authors.lastname: Serly
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Ean-Jeong
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Department of Organic Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Irén
authors.initials: I
authors.lastname: Vincze
authors.affiliation: Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Somlai
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Mohamed E M
authors.initials: ME
authors.lastname: Saeed
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary molnar.jozsef@med.u-szeged.hu efferth@uni-mainz.de.
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany molnar.jozsef@med.u-szeged.hu efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism*; D000079923:Copper Transporter 1; D016503:Drug Delivery Systems; D004351:Drug Resistance; D006801:Humans; D062105:Molecular Docking Simulation / Q000379:methods*; D009369:Neoplasms / Q000401:mortality*
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1
keywords: Cancer; copper transporter; drug resistance; molecular docking