ABSTRACT
The 2-furfural semicarbazone and thiosemicarbazone copper and cobalt complexes demonstrated potent cytotoxicity against the growth of suspended leukemias and lymphomas as well as human lung MB9812, colon SW480, ovary 1-A9 and HeLa-S3 uterine carcinoma. In L1210 lymphoid leukemia cell the complexes inhibited preferentially DNA synthesis over 60 min at 25 to 100 microM. The copper and cobalt complexes functioned by multiple mechanisms to suppress synthetic steps in nucleic acid metabolism to reduce deoxynucleotide pools for incorporation into DNA. At high concentrations the complexes suppressed human DNA topoisomerase II activity with DNA nicks and DNA fragmentation but they did not alkylate the bases of DNA, cause intercalation between base pairs or cause cross-linking of DNA strands.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cobalt/chemistry , Copper/chemistry , DNA, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Enzyme Inhibitors/pharmacology , Furaldehyde/analogs & derivatives , Furaldehyde/chemical synthesis , Furaldehyde/pharmacology , Humans , Semicarbazones/chemical synthesis , Semicarbazones/pharmacology , Spectrophotometry, Ultraviolet , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/pharmacology , Topoisomerase I Inhibitors , Tumor Cells, CulturedABSTRACT
The human colon adenocarcinoma-derived cell line CaCo-2 was used as a model system to study the effects of copper (II), tetradentate N-alkyl ligand (H2L) and their complex. The stimulatory effect of the complex was obtained with lower concentrations from 10(-7) to 10(-17) mol.L-1, while inhibiting effects occur from 10(-4) to 10(-6) mol.L-1. According to this study, copper (II) and free ligand were toxic for cultured cells. Our data suggested that the complex, according to our toxicity assays in mice, could be used as an antimitotic agent.
