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Molecular Docking Analysis of Steroid-based Copper Transporter 1 Inhibitors
Onat Kadioglu1, Julianna Serly2, Ean-Jeong Seo1
1Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
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.
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