Abstract
Aims and Objective: A series of novel phthalazine derivatives was synthesized with versatile, readily accessible electrophilic and nucleophilic reagents. The newly synthesized compounds were confirmed by the results of spectroscopic measurements. Hence, their potential clinical application investigated in particular for cancer treatment.
Materials and Methods: The newly synthesized compounds were characterized by spectroscopic measurements and were tested for their in vitro anticancer activity by MTT assay against human liver cancer cell line. Docking study of all the synthesized compounds was performed within the active site of the enzyme VEGFR-2 (Vascular Endothelial Growth Factor Receptor-2).
Results: The quinazoline derivative 12 emerged as the most potent compound in this study with an IC50 value of 5.4 µM. Docking study showed that the synthesized compounds were fit in the VEGFR-2 active site almost at the same position of sorafenib and vatalanib with comparable docking scores (-15.20 to -8.92 was kcal/mol).
Conclusion: we have synthesized a novel series of phthalazine derivatives and evaluated their potential anticancer activity against HEPG2 cell line. The quinazoline derivative 12 emerged as the most potent compound in this study with an IC50 value of 5.4 µM. The SAR and docking studies pointed out that rigidification of the structure resulted in better activity and better binding within the active site of VEGFR-2 as in compounds 3, 5, 6 and 12. These results introduced new phthalazine derivatives having promising activity which could lead to the development of more potent anticancer agents.
Keywords: Phthalazine, tetrahydrophthalazin, 1, 4-dichlorophthalazin, phthalazino[1, 2-b]quinazoline, docking, anticancer.
Graphical Abstract
Call for Papers in Thematic Issues
Exploring the Role of Chemical Graph Theory in Advancing Current Organic Synthesis
Organic synthesis is a fundamental discipline in chemistry, crucial for the creation of complex molecules with diverse applications in pharmaceuticals, materials science, and beyond. However, the process of designing efficient synthetic routes for target molecules remains challenging. Chemical graph theory, a branch of theoretical chemistry, offers powerful tools for understanding ...read more
Photoswitches for Molecular Recognition
This Special Issue would cover the hot topics on synthesis and chemical and photophysical characterization of new photoswitchable derivatives and their applications on molecular recognition of metabolites and biological active compounds, both in physiological medium and in living cells. Photoswitches are compounds that can change their conformation or properties in ...read more
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