Design, docking, MD simulation and in-silco ADMET prediction studies of novel indolebased benzamides targeting estrogen receptor alfa positive for effective breast cancer therapy

Warude B. J., Wagh S. N., Chatpalliwar V. A., YILDIRIM M., ÇELİK İ., Rudrapal M., ...Daha Fazla

Pharmacia, cilt.70, sa.2, ss.307-316, 2023 (ESCI) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 70 Sayı: 2
  • Basım Tarihi: 2023
  • Doi Numarası: 10.3897/pharmacia.70.e100356
  • Dergi Adı: Pharmacia
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Central & Eastern European Academic Source (CEEAS), EMBASE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.307-316
  • Anahtar Kelimeler: bazedoxifene, benzamide, breast cancer, docking, estrogen receptor alpha, indole scaffold, molecular dynamics, swiss admet
  • Erciyes Üniversitesi Adresli: Evet

Özet

Breast cancer is one of the most common malignancies in women, afflicting millions of lives each year. Our current study suggests that the development of the most promising 7-substituted -1-(4-(piperidine-1-yl methoxy)benzyl)-1H-indole-3-carboxamide derivatives results in potent anticancer agents through in-silico investigations. The molecular docking was performed against estrogen receptor alpha (ER-α) positive (PDB ID: 3UUD) of breast cancer cells to anticipate the binding modes of the designed compounds and the likely mode of action. The interactions between the ligands and amino acid residues were thoroughly elucidated. The stability of the docked protein-ligand complexes was further confirmed by 100 ns molecular simulations methods. From in-silico studies, indole-based benzamides exhibited satisfactory physicochemical, drug-likeness and toxicity properties. To conclude, the most promising substituted benzamide analogs on the indole ring could serve as a possible modulator against ER-α positive breast cancer.