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Several derivatives and analogs of the recently reported antiproliferative and antitumor agent trans-bis(salicylaldoximato) copper(II) (CuSAO 2 ) have been prepared and tested for antiproliferative activity against L1210 leukemia cells in vitro. The salicylaldimine analog of CuSAO 2  had a very strong antiproliferative activity, the 2-day IC 50  value being lower than 3 μg/ml- The 2,3-dihydroxybenzaldoxime analog was equally active with CuSAO 2 , while the corresponding 2,5-dihydroxy derivative had a slightly lower activity. The 2,3,4-trihydroxybenzaldoxime derivative had a much lower activity than had the dihydroxybenzaldoxime derivatives. The zinc(II) analog of CuSAO 2  had only a low antiproliferative activity. The ligand of CuSAO 2 , salicylaldoxime, resembles pyridoxal oxime, a vitamin B 6  antagonist and a powerful inhibitor of pyridoxal kinase. An attempt to reduce the toxicity of CuSAO 2  in vivo with pyridoxal hydrochloride led to increased toxicity.

Antiproliferative Activity of Derivatives of trans-Bis(salicylaldoximato)copper(II) in vitro. Some in vivo Properties of the Parent Compound