Curcumin as a natural compound is made of various components including protein, carbohydrate, and curcuminoid. Curcuminoid is made of curcumin, desmethoxycurcumin and bis desmethoxycurcumin. Curcumin is used for the treatment of cancer and inflammatory disorders, but it has some therapeutic problems like poor bioavailability, poor efficacy, and chemical instability. To overcome these problems, the objective of this study is (1) synthesis of pyrazole curcumin analogs, (2) synthesis of triazole curcumin analogs, and (3) in-vitro study of the anticancer activity of these curcumin analogs on head & neck, breast, pancreatic and glioblastoma cancer cells. During this part of my Ph.D. project, we have synthesized 9 pyrazole and 4 triazole curcumin analogs and studied their anticancer activity against CAL 27 and UM-SCC-74A as head & neck cancer cell lines, MDA-MB-231 as breast cancer cell line, HPAF as pancreatic cancer cell line, and MG118 as glioblastoma cancer cell lines. We have studied the effect of these analogs on head & neck cancer cell lines by using cell proliferation assay and western blotting analysis. Compound 49 was shown the best anticancer activity on these cancer cell lines. Western blotting analysis revealed that compounds 49, 81, and 77, showed anticancer activity. We did MTS assay study on MDA-MB 231 as a human cancer cell line and the study revealed that compounds 6 and 81 had good anticancer activity against these cancer cell lines, while triazole analogs showed weak anticancer activity. We also used MTS assay study to investigate the effect of curcumin analogs. Compounds 6 and 86 showed good anticancer activity against HPAF cell line. Cell Titer Glo-2 assay study on MG118 cell line revealed that compounds 49, 51, and 80 had good anticancer activity against glioblastoma cancer cell lines. The expression of the CXCR4 gene leads to making a CXCR4 protein which is a GPCR protein. Research showed that this protein is involved in different cancer types. Overexpression of CXCR4 leads to cancer metastasis. The objective of this study as the second part of my Ph.D. project is the discovery of novel hit molecules targeting CXCR4. We did the virtual screening of 229358 natural product compounds. Based on the crystallography structure, we generated the receptor file. FRED docking led to the identification of 500 hit compounds out of 229358 compounds. 500 hit compounds were filtered based on several parameters which led to the identification of 4 hit molecules. Root Mean Square Deviation study has shown that two of these hit molecules stabilized the protein Structure. Moreover, based on the Radius of the gyration study, three of these molecules maintain the compactness of protein. The hydrogen bond study of these complexes showed that two complexes made hydrogen bonds with targets. So, molecular dynamic analysis by Gromacs led to the identification of 2 hit molecules for CXCR4 antagonist activity. Keywords: Curcumin, Cancers, In-vitro study
