Anticancer Activity Screening of a Series of Imidazo[2,1-c] [1,2,4]triazolone and Imidazo[1,2-b][1,2,4]triazolone Derivatives Synthesized Under Solvent Free Conditions

摘要

In this approach we applied a green synthetic protocol for the preparation of a novel series of imidazotriazole derivatives under solvent free conditions and shorter reaction times utilizing the reactive 2-thioxoimidazolidinone derivative 1 as a starting substrate. Different substituted imidazo[2,1-c][1,2,4] triazolone derivatives 2-4,6 and imidazo[1,2-b][1,2,4]triazolone derivatives 8-10, 12, 13, 15, 16 and 18 were synthesized. We carried out the synthesis of the open chain analogues phenyl-imidazolidin-2-ylidenepicolinohydrazide 5, dihydroimidazolyla-cetamide 11, imidazolylpicolinamide 14, pentahydroxyhexylide-neaminoimidazol-5-one derivative 17, dihydroimidazolyl-N,N-dimethylformimidamide 19 and the dihydroimidazo[1,2-b] [1,2,4]triazepine-7-carbonitrile 20. The synthetic methods involved mainly fusion of compound 1 with the appropriate reagents. The in vitro anticancer evaluation at the National Cancer Institute (NCI), USA at a single dose (105 M) in full NCI 60 cell panel revealed that a significant inhibition for some cancer cells was observed with compounds 11 and 17-19 (38-67.5% inhibition).These novel compounds displayed appreciable anticancer activities against different cancer cell lines including leukemia, colon cancer, melanoma, ovarian cancer, renal cancer and non-small cell lung cancer cell lines.