GdCl3 promoted synthesis of novel pyrimidine fused indazole derivatives and their anticancer activity

The three component Grieco condensation of indazoles, aliphatic/aromatic aldehydes, and electron rich olefins in the presence of GdCl3 resulted in a novel pyrimidine fused indazoles in single pot under mild conditions. Representative examples were screened for in vitro anti-cancer activity and some of the compounds exhibited promising cytotoxic activity against U937 cell lines in comparable with standard drug etoposide. The data were further compared with structure-based investigations using docking studies with the crystal structure of Rho-kinase (2F2U) protein. The fitness values estimated by genetic algorithm were found to have a good correlation with the experimental inhibitory potencies.