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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.

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