Synthesis of certain 1,3,5-trisubstituted pyrazole derivatives of potential anticancer activity / Mennatullah Nagy Abdelhamed ; Supervised Safinaz Elsayed Abbas , Riham François George , Eman Mohamed Samir

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

Cancer is the second cause of mortality after cardiac diseases in the world. It is continuing to act as a major problem of health in both developing and developed countries. Therefore, there is a continuous need to search of new anticancer hits that inhibit different targets leading to more efficacies and less side effects compared to the traditional agents.Literature cited that pyrazoleand pyrazoline derivatives display a therapeutic activity as anticancer agents against breast, colon, lung, liver, cervical cancer by acting on variable targets through different mechanisms of action.Accordingly, the present study is concerned with the synthesis of new derivatives belonging to 1,3,5-trisubstituted pyrazole/pyrazolinesVIa,b,VII, VIIIand substituted thiazolylpyrazolinesXa-d, XIIa-c,XIVa-d. This is achieved via two intermediates, namely: 2-chloro-6-methoxy quinolin-3-yl chalcone IV and 5-(2-chloro-6-methoxyquinolin-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide VIb. The newly synthesized compoundswere evaluated for their in vitro cytotoxicity against three human cancer cell lines namely: MCF7 (breast), Hela (cervical), DLD1 (colon) in addition to normal fibroblast cell (WI38) relative to CHS 828 as a reference compound. Compounds eliciting superior anticancer activity were screened their EGFR inhibitory activity compared to gefitinib.Moreover a molecular docking study was performed on compounds exhibiting significant EGFR inhibitory activity to find their binding mode in the active site of the enzyme

Issued also as CD