Design and prediction of novel pyrazole derivatives as potential anti-cancer compounds based on 2D-QSAR study against PC-3, B16F10, K562, MDA-MB-231, A2780, ACHN and NUGC cancer cell lines
Fatima Ezzahra Bennani,
Latifa Doudach,
Khalid Karrouchi,
Youssef El rhayam,
Christopher E. Rudd,
M’hammed Ansar,
My El Abbes Faouzi
Affiliations
Fatima Ezzahra Bennani
Laboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, BP6203, Rabat, Morocco; Laboratory of Analytical Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, BP6203, Rabat, Morocco; Division of Immunology-Oncology, Centre de Recherche Hôpital Maisonneuve-Rosemont (CR-HMR), Montreal, QC, Canada; Corresponding author.
Latifa Doudach
Department of Biomedical Engineering Medical Physiology, Higher School of Technical Education of Rabat, Mohammed V University in Rabat, BP6203, Rabat, Morocco
Khalid Karrouchi
Laboratory of Analytical Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, BP6203, Rabat, Morocco
Youssef El rhayam
Agro-Resources Laboratory, Organic Polymers and Process Engineering (LRGP) / Organic and Polymer Chemistry Team (ECOP), Faculty of Sciences Ibn Tofail University, Kenitra, Morocco
Christopher E. Rudd
Division of Immunology-Oncology, Centre de Recherche Hôpital Maisonneuve-Rosemont (CR-HMR), Montreal, QC, Canada; Department of Microbiology, Infection and Immunology, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada; Division of Experimental Medicine, Department of Medicine, McGill University Health Center, McGill University, Montreal, QC, Canada
M’hammed Ansar
Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, BP6203, Rabat, Morocco
My El Abbes Faouzi
Laboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, BP6203, Rabat, Morocco
Despite the decades of scientific studies for developing promising new therapies, cancer remains a major cause of illness and mortality, worldwide. Several cancer types are the major topic of research in drug discovery programs due to their global incidence cases and growing frequency. In the present study, using two different statistical approaches PCA (principal component analysis) and PLS (partial least squares), six 2D-QSAR (quantitative structure activity relationship) models have been developed for the set of compounds retrieved against seven cancer cell lines vizPC-3, B16F10, K562, MDA-MB-231, A2780, and ACHN. For the creation and validation of 2D-QSAR models, OECD (Organization for Economic Co-operation and Development) requirements have been strictly followed. All of the generated 2D-QSAR models produce a significant and high correlation coefficient value with several other statistical parameters. Moreover, developed 2D-QSAR models have been used for activity predictions of in-house synthesized 63 pyrazole derivatives compounds. Precisely, most statistically significant and accepted2D-QSAR model generated for each cancer cell line has been used to predict the pIC50 value (anti-cancer activity) of all 63 synthesized pyrazole derivatives. Furthermore, designing of novel pyrazole derivatives has been carried out by substituting the essential functional groups based on the best derived 2D-QSAR models for each cancer cell line, more precisely, based on the most significant molecular descriptors with enhanced anti-cancer activity. Finally, the prediction of the new designed molecules reveals higher pIC50 than the standard compounds.
