Published May 11, 2023 | Version v1
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Design, docking, MD simulation and in-silco ADMET prediction studies of novel indole-based benzamides targeting estrogen receptor alfa positive for effective breast cancer therapy

  • 1. S.N.J.B's S.S.D.J. College of Pharmacy, Chandwad, India|D Y Patil University, Pune, India
  • 2. S.N.J.B's S.S.D.J. College of Pharmacy, Chandwad, India
  • 3. Erciyes University, Kayseri, Turkiye
  • 4. School of Biotechnology and Pharmaceutical Sciences, Vignan's Foundation for Science, Technology & Research, Guntur, India
  • 5. Majmaah University, Al Majmaah, Saudi Arabia|Majmaah University, Al Majmaah, Saudi Arabia
  • 6. M. S. Ramaiah Institute of Technology, Bengaluru, India
  • 7. Rashiklal M. Dhariwal Institute of Pharmaceutical Education and Research, Pune, India

Description

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.

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