Annelation of substituted 3-Hydrazinylimidazo [2,1-c] [1,2,4]triazolone to a series of fused [1,2,4]triazepine and [1,2,4]triazine analogues and evaluation of their anticancer activity

Abstract

Versatile straightforward synthetic pathways for a novel series of annelated imidazo [2,1-c] [1,2,4]triazole derivatives were performed. Our newly synthesized compounds were prepared from the reactive binucleophile 3-hydrazinyl-5-(4-methoxybenzylidene)-7-phenyl-5H-imidazo [2,1-c] [1,2,4] triazol-6(7H)-one 2 applying different synthetic strategies. The annelated derivatives are different imidazo [2′,1’:3,4] [1,2,4]triazolo [5,1-c] [1,2,4] triazepines 3–7; imidazo[2′,1’:3,4] [1,2,4]triazolo [5,1-c] [1,2,4,6]tetrazepine 8; imidazo[2′,1’:3,4] [1,2,4]triazolo [5,1-c] [1,2,4]triazines 9–15 and imidazo [1,2-d] [1,2,4]triazolo [4,3-b] [1,2,4]triazole analogue 16. Thirteen compounds have been subjected to screening for in vitro anticancer activity. This screening had been conducted at the National Cancer Institute (NCI), USA at a single dose (10-5 M) against full NCI 60 cell panel. The screening results indicated a considerable anticancer activity for compounds 7 and 13 against CNS cancer (SNP-75) cell line with growth inhibition percent 46.56 and 42.27, respectively. Moreover, a moderate anticancer activity against renal Cancer (UO-31) cell line was common with compounds 2, 7, 9, 11, 12, 13 and 15 with growth inhibition percent 31.54–39.52.