Synthesis and Structure-Activity Relationship; Exploration of some Potent Anti-Cancer Phenyl Amidrazone Derivatives

Background: Amidrazones have been reported to have significant anti-tumor properties against several cancer cell lines. Objectives: The current project aims to profile the structure-anticancer activity relationship of phenyl-amidrazons. Methods: Fifteen phenyl-amidrazone-piperazine derivatives were prepared and tested against four cancer cell lines (leukemia, prostate, breast and colon cancers). Results: Six compounds illustrated low micromolar anticancer IC50 values, while the remaining compounds were either inactive or of moderate potencies. All compounds were virtually nontoxic against normal fibroblast cells. Conclusion: Docking into the oncogenic kinase bcr/abl illustrated the critical importance of (i) phalogen substituent on the ligand's phenyl ring and (ii) the presence of positive ionizable moiety at the ligand's piperazine fragment for anticancer activity.