Utility of Certain 2-Furanone Derivatives for Synthesis of Different Heterocyclic Compounds and Testing their Anti-Cancer Activity.

BACKGROUND: 2-Furanones have attracted great attention due to their biological activities. They also have the ability to be converted to several biologically active heterocyclic and nonheterocyclic compounds, especially as anti-cancer agents. OBJECTIVES: This research aims to share in the development process of novel cytotoxic agents by synthesizing certain 2-furanone derivatives and using them as starting materials for the preparation of novel heterocyclic and non-heterocyclic compounds, then testing the synthesized derivatives for their anti-cancer activities. METHODS: All the newly synthesized compounds were fully characterized by elemental analysis, IR, Mass, and 1H-NMR spectroscopy. 18 synthesized compounds were selected by National Cancer Institute (NCI) for testing against 60 cell lines, and the active compound was tested as MAPK14 and VEGFR2-inhibitor using Staurosporine as standard. RESULTS: Compound 3a showed the higher activity against several cell lines; Leukemia (SR), Non- Small Cell Lung Cancer (NCI-H460), colon cancer (HCT-116), ovarian cancer (OVCAR-4), renal cancer (786-0, ACHN and UO-31) and, finally breast cancer (T-47D). It also has better inhibition activity against MAPK14 than the used reference. CONCLUSION: Compound 3a has promising anti-cancer activities compared to the used standards and may need further modification and investigations.

Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent and Evaluation for CDK2 Inhibition Activity.

BACKGROUND: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules; they can easily interact with biomolecules of living systems. OBJECTIVE: A series of substituted 2-thiobezimidazoles have been synthesized. Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell lines. METHODS: The spectral data of the synthesized compounds were characterized. A docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib, were performed. RESULTS: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in the CDK-ATP binding pocket .3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. CONCLUSION: Against all tested compounds; two compounds 3c &3l were found active against two types of cell-lines.