SYNTHESIS OF NEW 2, 5, 6-SUBSTITUTED IMIDAZO[2,1-B][1,3,4]THIADIAZOLE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS

摘要

A series of 2-cyclopropylimidazo [2,1-b] [1,3,4] thiadiazole derivatives 5(a-i) have been synthesized by reacting 5-cyclopropyl-1,3,4-thiadiazol-2-amine (3) and an appropriate 2-bromo-1,2-(substituted aryl) ethanones 4(a-i). Structures of these compounds were recognized by IR, 1 H NMR, 13 C NMR spectroscopy and Mass spectrometry. Hypoxia-inducible factor (HIF) has been identified as an important cancer drug target. HIF transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes, including angiogenesis and erythropoiesis. Here we analyzed the capacity of synthesized molecules to inhibit hypoxia-inducible factor prolyl hydroxylase (PHD2) in-silico as well as an in-vitro assay. Four 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,2-Cyclopropyl-6-(4-methoxyphenyl)-5-phenylimidazo[2,1-b][1,3,4]thiadiazole 5a (NSC D-754956/1) was found to be the most active candidate of the series at five dose level screening with a degree of selectivity toward leukemic cancer cell line.