Antiproliferative activity of derivatives of trans-bis(salicylaldoximato)copper(II) in vitro. Some in vivo properties of the parent compound.
Several derivatives and analogs of the recently reported antiproliferative and antitumor agent trans-bis(salicylaldoximato)copper(II) (CuSAO2) have been prepared and tested for antiproliferative activity against L1210 leukemia cells in vitro. The salicylaldimine analog of CuSAO2 had a very strong antiproliferative activity, the 2-day IC50 value being lower than 3 micrograms/ml. The 2,3-dihydroxybenzaldoxime analog was equally active with CuSAO2, 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 CuSAO2 had only a low antiproliferative activity. The ligand of CuSAO2, salicylaldoxime, resembles pyridoxal oxime, a vitamin B6 antagonist and a powerful inhibitor of pyridoxal kinase. An attempt to reduce the toxicity of CuSAO2 in vivo with pyridoxal hydrochloride led to increased toxicity.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000627:therapeutic use / Q000633:toxicity*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009942:Organometallic Compounds / Q000627:therapeutic use / Q000633:toxicity*; D013329:Structure-Activity Relationship; D015032:Zinc / Q000627:therapeutic use / Q000633:toxicity*
D009942:Organometallic Compounds; C046547:bis(salicylaldoximato)copper(II); D003300:Copper; D015032:Zinc