In Vitro and In Silico Determination of Some N-ferrocenylmethylaniline Derivatives as Anti-Proliferative agents Against MCF-7 Human Breast Cancer Cell Lines

Zegheb N., Boubekri C., Lanez T., Lanez E., Kucukkilinc T. T., Oz E., ...Daha Fazla

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, cilt.22, sa.7, ss.1426-1437, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 7
  • Basım Tarihi: 2022
  • Doi Numarası: 10.2174/1871520621666210624141712
  • Dergi Adı: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1426-1437
  • Anahtar Kelimeler: N-ferrocenylmethylaniline, breast cancer, MCF-7, MDA-MB-231, estrogen receptor, progesterone receptor, QSAR, antiproliferative activity, ACTIVITY-RELATIONSHIP QSAR, FERRICENIUM COMPLEXES, MOLECULAR DOCKING, DFT CALCULATIONS, DNA-BINDING, ESTROGEN, LIGAND, PROGESTERONE, ANTIESTROGENS, TRASTUZUMAB
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Background: Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7). Objective: In this study, we aimed to find new ferrocene derivatives having pharmacochemistry properties as potential drugs against human breast cancer cells. Methods: A series of 29 N-ferrocenylmethylaniline derivatives A0-A28 were synthesised, and their anti-proliferative activity against both hormone-dependent (MCF-7) and independent (MDA-MB 231) human breast cancer cell lines were performed using the MTT test. Molecular docking and drug-likeness prediction were also performed for the five most active derivatives towards MCF-7. A QSAR model was also developed for the perdition of the anti-proliferative activity against MCF-7 cell lines using molecular descriptors and MLR analysis. Results: All studied derivatives demonstrated better cytotoxicity against MCF-7 compared to the MDA-MB-231 cell lines, and compounds A2, A9, A14, A17 and A27 were the most potent ones but still less active than the standard anti-cancer drug, crizotinib. The QSAR study revealed good predictive ability, as shown by R-2 (cv) = 0.848. Conclusion: In vitro and in silico results indicated that derivatives A2, A9, A14, A17, and A27 possess the highest anti-proliferative activity; these results can be used to design more potent N-ferrocenylmethylaniline derivatives as anti-proliferative agents.