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

Abstract

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.

Imidazo[1,2,4]triazolone and fused imidazo[1,2,4]triazolone derivatives: Synthesis, in vitro anticancer screening, CDK2 inhibitory activity, and molecular modeling studies

“…Moreover, relying on the recorded moderate anticancer activity of the imidazotriazole derivative 9 against various NCI cell lines [27], our work was designed to annelate several heterocyclic systems to compound 9 . The study also involved evaluation of the anticancer activity of the newly obtained analogues.…”

“…The synthetic strategies adopted to acquire our new scaffolds are presented in Schemes 1-3. We used the imidazotriazole derivatives 2 and 9 [27] as templates for annulation of different bioactive heterocyclic rings.…”

“…In continuation of our work for the synthesis of anticancer imidazotriazole derivatives [27,28], we report herein the synthesis of new series of substituted and fused imidazotriazole scaffolds starting from compounds 2 and 9 with evaluation of their anticancer properties. The building core compound 2 was previously reported by our team to possess moderate activity against renal cancer UO-31 (33.25%) [27]. In this work, we aimed to study the effect of attachment of heterocyclic side chain at C 2 of compound 2, as in compounds 3, 4 and 5.…”

“…We have previously reported the synthesis and the promising anticancer activity of some novel imidazotriazol hybrids [27,28]. In light of the completion of our research dealing with the imidazotriazole nucleus, we report herein the synthesis of an additional series of substituted and fused imidazotriazole derivatives as roscovitine bioisosteres in order to study their CDK2 inhibitory and anticancer activities (Figure 3).…”

Synthesis, Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

“…Based on the idea of hybrid compounds [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], we reasoned that compounds incorporating both the imidazoline and triazole pharmacophore groups could be effective as chemotherapeutic agents. It should be pointed out that the imidazo-triazole moiety is a recurring motif of synthetic compounds of pharmacological interest [ 30 , 31 ]. The antiproliferative effects of the imidazo-triazole derivatives may result from inhibition of EPH-B3 and FGF-R1 tyrosine kinases [ 32 ].…”