One-pot, four-component synthesis and SAR STUDIES of spiro[pyrimido[5,4-b]quinoline-10,5'-pyrrolo[2,3-d]pyrimidine] derivatives catalyzed by beta-cyclodextrin in water as potential anticancer agents

摘要

Novel series of one-pot four component spiro[pyrimido[5,4-b]quinoline-10,5'-pyrrolo[2,3-d]pyrimidine] derivatives 4a-t were designed, synthesized, and identified by IR, H-1 NMR, C-13 NMR, Mass spectra and elemental analysis as well as evaluated for their anticancer activity against four human cancer cell lines, prostate cancer cell lines (PC-3), prostate cancer cell lines (DU-145), breast cancer cell lines (MDA-MB-231) and normal prostate epithelial cells (RWPE-1) by MTT assay, Compounds 4b, 4c, 4g and 4h showed the highest anticancer activities against both PC-3 and DU-145 prostate cancer cell with IC50 of 15.36, 19.92, 18.37, 14.46, and 16.50 mu M, respectively, and MDA-MB-231 breast cancer cells with IC50 of 10.64, and 7.97 mu M, respectively, in comparison to sunitinib as reference drug with IC50 of 19.62, 16.38 and 7.44 mu M, respectively. Furthermore, structure-activity relationship studies were performed for all synthesized compounds which predict that new analogue 4c was probe the importance of the spiro-oxindole moiety of the molecule by replacing the heterocyclic aniline in spiro-oxidole.