Identification of Potential C-kit Protein Kinase Inhibitors Associated with Human Liver Cancer: Atom-based 3D-QSAR Modeling, Pharmacophores-based Virtual Screening and Molecular Docking Studies

Koffi Alexis Respect Kouassi¹, Adenidji Ganiyou^2, , Anoubilé Benié^{1, 3}, Mamadou Guy-Richard Koné¹, N’Guessan kouakou Nobel¹, Kouadio Valery Bohoussou¹ and Wacothon Karime Coulibaly⁴

¹Laboratoire de Thermodynamique et de Physico-Chimie du Milieu, UFR SFA, Université Nangui Abrogoua, 02 BP 801 Abidjan 02, Côte d’Ivoire

²Laboratoire de Chimie Organique et de Substances Naturelles, UFR-SSMT, Université Félix Houphouët-Boigny 22 BP 582 Abidjan 22, Côte d’Ivoire

³Laboratoire de Chimie BioOrganique et de Substances Naturelles, UFR-SFA, Université Nangui Abrogoua, 02 B.P. 801 Abidjan 02 Côte-d’Ivoire

⁴UFR des Sciences Biologiques, Université de Péléforo Gon Coulibaly, Korhogo, BP 1328, Cote d'Ivoire

Cite this paper:
Koffi Alexis Respect Kouassi, Adenidji Ganiyou, Anoubilé Benié, Mamadou Guy-Richard Koné, N’Guessan kouakou Nobel, Kouadio Valery Bohoussou and Wacothon Karime Coulibaly. Identification of Potential C-kit Protein Kinase Inhibitors Associated with Human Liver Cancer: Atom-based 3D-QSAR Modeling, Pharmacophores-based Virtual Screening and Molecular Docking Studies. American Journal of Pharmacological Sciences. 2021; 9(1):1-29. doi: 10.12691/ajps-9-1-1

Abstract

Rhodanine and its derivatives exhibit interesting biological activities as well as a wide range of biological applications. In this study, a dataset of seventy-four molecules with anticancer activities against human cancer cell line Huh-7D12, were chosen for the modeling of pharmacophores and Quantitative Structure Activity (3D-QSAR) relationship. Pharmacophoric models containing five sites were generated from three characteristics: hydrogen bond acceptor (A), hydrophobic (H) and aromatic ring (R). After the validation, eight hypotheses which presented a good power of selectivity of the active agents were selected (GH > 0.5). Internal and external validation parameters indicated that the generated 3D-QSAR model exhibits good predictive capabilities and significant statistical reliability (R² = 0.9606, Q² = 0.955, = 0.952). Pharmacophoric models and contour maps provided significant information on the main structural features of rhodanine derivatives. Twenty-one molecules were returned from the Enamine chemical database after molecular docking studies (HTVS, SP, XP, and IFD). These provided an estimate of ligand-protein binding interactions essential for anticancer activity. The ADMET prediction of these 21 compounds suggested that their pharmacophoric properties lie within an acceptable range. This result indicates that these new compounds provide an effective basis for the methodical development of potent inhibitors of the protein kinase C-kit.

Keywords:
Rhodanine derivatives 3D-QSAR Pharmacophore Molecular Docking ADMET

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