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<p>Quinoline derivatives are valuable pharmacophores in medicinal chemistry with a wide range of biological activities. A dataset of 36 cancer inhibitors (numbered from 7 to 42) was investigated in silico to discover new drug candidates and gain insights into their interactions with two major breast cancer target receptors, ER-α and ER-β. Molecular docking results showed that compound 41 (5-(dimethylamino)naphthalene-1-sulfonic acid [3-[7-(trifluoromethyl)quinolin-4-ylamino]propyl]amide) and compound 35 (4-methyl-<i>N</i>-[3-[7-(trifluoromethyl)quinolin-4-ylamino]propyl] benzenesulfonamide) and their analogs exhibited good docking values within the binding sites of ER-α and ER-β targets, respectively, compared with the complexes formed with standard references, with many interactions. Molecular dynamics (MD) simulations indicated that compounds 41 and 35 exhibited overall comparable binding behaviors with both targets, which was supported by RMSD, RMSF, <i>R</i><sub>g</sub>, and SASA analyses. Bioisosteric substitution techniques were applied to compounds 41 and 35 to generate analogs with improved physicochemical and pharmacological properties due to their less than ideal hydrogen bonding properties compared to standard compounds. Drug-likeness property was confirmed by applying Lipinski, Veber, and Egan rules to compounds 41 and 35 and their analogs to evaluate anti-breast cancer efficacy. These findings can facilitate pharmaceutical research as the identified compounds represent promising candidates for the treatment of breast cancer. The compounds investigated in this study can provide a valuable framework for further optimization and development, paving the way for the development of new therapeutic strategies for breast cancer.</p> Graphical abstract <p></p>

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Molecular modeling studies of novel breast cancer inhibitors using molecular docking, molecular dynamics, MEP, bioisosteric replacement, and ADME-Tox prediction

  • 期刊论文

  • 发表日期：

    2026年3月17日

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  • Ferdaous Hasni,
  • Ismail Daoud,
  • Nadjib Melkemi,
  • Samir Kenouche,
  • Thamer Alorini,
  • Mohammed Baqur S. Al-Shuhaib

摘要

Quinoline derivatives are valuable pharmacophores in medicinal chemistry with a wide range of biological activities. A dataset of 36 cancer inhibitors (numbered from 7 to 42) was investigated in silico to discover new drug candidates and gain insights into their interactions with two major breast cancer target receptors, ER-α and ER-β. Molecular docking results showed that compound 41 (5-(dimethylamino)naphthalene-1-sulfonic acid [3-[7-(trifluoromethyl)quinolin-4-ylamino]propyl]amide) and compound 35 (4-methyl-N-[3-[7-(trifluoromethyl)quinolin-4-ylamino]propyl] benzenesulfonamide) and their analogs exhibited good docking values within the binding sites of ER-α and ER-β targets, respectively, compared with the complexes formed with standard references, with many interactions. Molecular dynamics (MD) simulations indicated that compounds 41 and 35 exhibited overall comparable binding behaviors with both targets, which was supported by RMSD, RMSF, Rg, and SASA analyses. Bioisosteric substitution techniques were applied to compounds 41 and 35 to generate analogs with improved physicochemical and pharmacological properties due to their less than ideal hydrogen bonding properties compared to standard compounds. Drug-likeness property was confirmed by applying Lipinski, Veber, and Egan rules to compounds 41 and 35 and their analogs to evaluate anti-breast cancer efficacy. These findings can facilitate pharmaceutical research as the identified compounds represent promising candidates for the treatment of breast cancer. The compounds investigated in this study can provide a valuable framework for further optimization and development, paving the way for the development of new therapeutic strategies for breast cancer.

Graphical abstract