Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

The present investigation deals with the synthesis of pyrazolylbenzimidazoles with bi substituents at both the benzimidazole and pyrazole moieties. All the synthesized compounds were tested for their ability to inhibit Sphingosine-1 kinase (SphK-1) which promotes tumor growth and is considered as a novel approach for treatment of cancer. Most of the tested compounds showed good percentage of inhibition. In addition, fluorescence binding studies of all the synthesized compounds was performed and compounds130,131, 138, 142, 144, 146,147, 148 and 150 revealed the formation of a stable protein-ligand complex. The IC50 of the nine compounds were calculated. In addition, the antiproliferative activity against 60 different cell lines were determined by NCI Development therapeutic program and the results showed that these compounds showed good inhibition percentage against different cell lines. Finally, molecular docking study was performed in the active site of SphK-1 to elucidate the mode of interaction

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