Comparative analysis of the cytotoxicity of substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)] copper(II) chelates. 2. Parabolic correlations and their implications for selective toxicity.
The synthesis of an extended series of para-substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)] copper(II) chelates is reported. Subsequent biological evaluation and regression analysis have been performed, correlating pI50 with extrathermodynamic substituent parameters. Parabolic correlations with pi have resulted which predict optimum lipophilic character of the para substituent with respect to Ehrlich ascites cytotoxicity (pi0 = -2.13) and with respect to ascites vs. liver slice cytotoxicity (pi0 = -1.31). Results indicated clearly that the chelate most toxic to the tumor cell model may not be the most selective.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D002614:Chelating Agents; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D003300:Copper