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Abstract
To design and synthesize novel pyrazole-linked norcanthridin analogs and their disodium phosphates by [3+2]1, 3-dipolar cycloaddition reaction of norcantharidin derivatives of substituted aromatic amines with three hydrazines. All analogues have been screened for their antiproliferative activity in vitro against a panel of tumor cell lines: KB, SMMC-7721, SGC7901, ECA109, HO-8910, K562, A549 and MCF-7 producing IC50 values from 0.07 μM to > 100 μM. Compound 8c showed potency for the treatment of hepatoma, with IC50 value to SMMC-7721 cell line comparable to that of norcantharidin. High potency and selectivity of compound 12 to MCF-7 cell line prove that the phosphorylation of norcantharidin analogs is an effective way to increase the activity and solubility.
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