Cytotoxicity of copper and cobalt complexes of furfural semicarbazone and thiosemicarbazone derivatives in murine and human tumor cell lines.
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.
Hall
I H
IH
Division of Medicinal Chemistry & Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, USA. iris_hall@unc.edu
Lackey
C B
CB
Kistler
T D
TD
Durham
R W
RW
Jouad
E M
EM
Khan
M
M
Thanh
X D
XD
Djebbar-Sid
S
S
Benali-Baitich
O
O
Bouet
G M
GM
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004273:DNA, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005662:Furaldehyde / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D012664:Semicarbazones / Q000138:chemical synthesis / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D012664:Semicarbazones; D013882:Thiosemicarbazones; D059004:Topoisomerase I Inhibitors; D003035:Cobalt; D003300:Copper; D005662:Furaldehyde