Authors: Khadijah Saghiri | Ismail Daoud | Nadjib Melkemi | Fouzia Mesli | H Sung | J Ferlay | R Siegel | M Laversanne | I Soerjomataram | A Jemal | F Bray | N Harbeck | F Penault-Llorca | J Cortes | M Gnant | N Houssami | P Poortmans | K Ruddy | J Tsang | F Cardoso | J Del Ro | M Alliende | N Molina | F Serrano | S Molina | P Vigil | H Kuhl | E Curtit | V Nerich | L Mansi | L Chaigneau | L Cals | C Villanueva | F Bazan | P Montcuquet | N Meneveau | S Perrin | Y Lu | Y Tong | X Chen | K Shen | K Chavez | S Garimella | S Lipkowitz | I Paterni | C Granchi | J Katzenellenbogen | F Minutolo | H Hua | H Zhang | Q Kong | Y Jiang | A Waks | E Winer | M Pagano | E Ortona | M Dupuis | R Cailleau | R Young | M Olive | Reeves | W Jr | H Soule | J Vazquez | A Long | S Albert | M Brennan | Coma | A Cimpean | M Raica | V Jordan | L Yin | J.-J Duan | X.-W Bian | S.-C Yu | D Sharma | S Kumar | B Narasimhan | H Patel | T Bihani | Z Wang | Z Ma | Z Shen | N Levy | S Paruthiyil | X Zhao | O Vivar | E Saunier | C Griffin | M Tagliaferri | I Cohen | T Speed | D Leitman | N Devi | K Kaur | A Biharee | V Jaitak | Y Cui | I Parra | M Zhang
Source: Biointerface Research in Applied Chemistry (article, 2022-03-28)
Field: Chemistry — Organic Chemistry

QSAR Study, Molecular Docking/Dynamics Simulations and ADME Prediction of 2-Phenyl-1H-Indole Derivatives as Potential Breast Cancer Inhibitors In the current investigation, QSAR studies have been performed on fifty-four analogs of the 2-phenyl-1H-indole analogs, which have antiproliferative activity against two cancer cells lines MDA MB231 and MCF-7.Partial least square (PLS) regression exhibited a good correlation between fitted and observed biological activities. The descriptive and predictive performances of QSAR models have been assessed and validated through internal and external validations. The leave-one-out cross-validation R2CV, the bootstrapping correlation coefficients R2boots and the predicted R2pred reveal a high predictive power for both models developed. Molecular docking/dynamics simulations results show that the ligands L39, L40, and L48 fit well in the pocket of the estrogen-α (PDB:1A52) and ligand L47 with the progesterone (PDB:1A28) confirmed by the high negative score values and by the several interactions ( H-bonds and hydrophobic interactions) which established between these ligands and the active site residues of both receptors. Finally, Drug-likeness and ADME prediction have revealed that the ligands L39, L40, and L48 complied with Lipinsky, Veber, and Egan rules that presented a good absorption and oral bioavailability, except the ligand L47. Clearly, this finding shows that these ligands could be used as potential precursors to developing breast cancer drugs. Quantitative structure–activity relationship ; ADME ; Protein Data Bank (RCSB PDB) ; Chemistry ; Indole test ; Docking (animal) ; Stereochemistry ; Cross-validation ; Molecular dynamics ; Computational biology ; Computational chemistry ; Biochemistry ; Biology ; Machine learning ; In vitro ; Medicine ; Computer science Synthesis and biological activity ; Computational Drug Discovery Methods ; Synthesis and Characterization of Heterocyclic Compounds