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 phenylimidazolidin-2-ylidenepicolinohydrazide 5, dihydroimidazolylacetamide 11, imidazolylpicolinamide 14, pentahydroxyhexylideneaminoimidazol-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 (10 À 5 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.

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In continuation of our program for synthesizing novel imidazotriazole scaffolds, we report herein the synthesis of new fifteen substituted and fused imidazotriazole derivatives via different addition and cyclocondensation pathways. Thirteen compounds have been tested for their antiproliferative activity against 60 NCI cell lines. Compounds 3, 15 and 17 were the most active among the synthesized series. Imidazo[2,1-c][1,2,4]triazolone derivative 3 showed high activity against leukemia K-562 (51.00%), RPMI-8226 (68.36%) and breast cancer MCF-7 (56.76%) cell lines. While compound 15 exhibited high potency against colon cancer HCT-15 (59.33%), CNS cancer SNB-75 (57.06%) and renal cancer UO-31 (50.5%) cell lines. Bis[1,2,4]triazolopurin-7-one derivative 17 showed strong activity against CNS cancer SNB-75 cell line (54.32%). Compounds 3, 15 and 17 were evaluated through molecular modeling and docking techniques to give us a closer look on their binding mode with CDK2. The in vitro inhibitory activity against CDK2 was also performed for compounds 3 and 17. Compound 3 was subjected to further investigations by studying its effect on cell cycle progression and cell apoptosis in MCF-7 cell line. It caused apoptosis, necrosis and induced cell cycle arrest at G2/M phase in MCF-7 cell.