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

摘要

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