Molecular docking analysis of steroid-based copper transporter 1 inhibitors

Onat Kadioglu, Julianna Serly, Ean Jeong Seo, Irén Vincze, Csaba Somlai, Mohamed E.M. Saeed, József Molnár, Thomas Efferth

Research output: Contribution to journalArticle

Abstract

Copper transporter 1 (CTR1) represents an important determinant of cisplatin resistance. A series of 35 semi-substituted steroids were recently investigated on cisplatinresistant 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.

Original languageEnglish
Pages (from-to)6505-6508
Number of pages4
JournalAnticancer research
Volume35
Issue number12
Publication statusPublished - Dec 2015

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Keywords

  • Cancer
  • Copper transporter
  • Drug resistance
  • Molecular docking

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kadioglu, O., Serly, J., Seo, E. J., Vincze, I., Somlai, C., Saeed, M. E. M., Molnár, J., & Efferth, T. (2015). Molecular docking analysis of steroid-based copper transporter 1 inhibitors. Anticancer research, 35(12), 6505-6508.