Design and synthesis of some novel quinoline derivatives as anticancer and radiosensitizing agents targeting VEGFR tyrosine kinase

Abstract

Abstract Quinoline derivatives posses many types of biological activities and have been reported to show significant anticancer activity. There is a variety of mechanisms for the anticancer activity and the most distinguished mechanism is the inhibition of vascular epithelial growth factor receptor tyrosine kinase (VEGFRTK). Novel quinoline derivatives 6 , 7a , 7b , 7c , 8 , 9 , 10 , 11 , 12 and pyrimido[4,5‐ b ]quinoline derivatives 16 , 17 , 18 , 19 , 20 are reported herein. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7) in which VEGFR is highly expressed. Compounds 6 and 7 with IC 50 values of 8.5 μ M and 21.9 μ M were the most active compounds and exhibited cytotoxic activities higher than that of the reference drug doxorubicin (IC 50 = 32.02 μ M ). The most active compounds 6 and 7 were further evaluated for their ability to enhance the cell killing effect of γ‐radiation. J. Heterocyclic Chem., (2011).