Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives

A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]-thiadiazole derivatives 4(a–k) have been prepared by reaction of 2-amino-5-cyclopropyl-1,3,4-thiadiazole and an appropriate phenacyl bromide. Further 5-bromo 5(a–k) and 5-thiocyanato 6(a–k) derivatives were synthesized in order to study the effect of these substituents on antitumor activity. Structures of these compounds were established by IR, 1H NMR, 13C NMR and Mass spectroscopy. Seven compounds were granted NSC code at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell panel. Among the compounds tested, 5-bromo-6-(4-chlorophenyl)-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole 5b (NSC D-96022/1) was found to be the most active candidate of the series at five dose level screening with degree of selectivity toward Leukemic cancer cell line.

The 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]-thiadiazole derivatives and their biological evaluation as antitumor agents using National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Figure optionsDownload as PowerPoint slideHighlights
► Synthesis and biological evaluation of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives as antitumor investigated.
► 5-Bromo-6-(4-chlorophenyl)-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole 5b (NSC D-96022/1) was the most active candidate.
► It shown degree of selectivity toward Leukemic cancer cell line (MG MID ratio: 3.6).