ABSTRACT
5-Methyl 2-furfuraldehyde thiosemicarbazone (M5HFTSC) with nickel(II) leads to three types of complexes: [Ni(M5HFTSC)(2)X(2)], [Ni(M5FTSC)(2)] and [Ni(M5FTSC)(2)] x 2DMF. In the first type the ligand remains in thione form, while in the two other, the anionic thiolato form is involved. The species [Ni(M5HFTSC)(2)X(2)] has been characterized spectroscopically. The structures of [Ni(M5FTSC)(2)] x 2DMF and [Ni(M5FTSC)(2)] have been solved using X-ray diffraction. Biological studies of [Ni(M5HFTSC)(2)Cl(2)] have been carried out in vitro for antifungal activity on human pathogenic fungi, Aspergillus fumigatus and Candida albicans, and in vivo for toxicity on mice. The results are compared to those of the ligand, the metal salt and a similar copper complex [Cu(M5HFTSC)Cl(2)].
Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Furaldehyde/analogs & derivatives , Nickel/pharmacology , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacology , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/pharmacology , Animals , Antifungal Agents/chemistry , Aspergillus fumigatus/drug effects , Candida albicans/drug effects , Crystallography, X-Ray , Furaldehyde/chemical synthesis , Furaldehyde/chemistry , Furaldehyde/pharmacology , Humans , In Vitro Techniques , Lethal Dose 50 , Ligands , Magnetic Resonance Spectroscopy , Male , Mice , Molecular Structure , Nickel/chemistry , Organometallic Compounds/chemistry , Spectroscopy, Fourier Transform Infrared , Thiosemicarbazones/chemistryABSTRACT
Potent cytotoxic copper(II) complexes of furannic semicarbazones were studied in ethanolic solutions at 25 degrees C. The four ligands used were synthesized in our laboratory, i.e. 2-furfural semicarbazone (FSC), 5-methyl 2-furfural semicarbazone (MFSC), 2-furfural 4-phenyl semicarbazone (FPSC) and 3-(2-furyl) prop-2-enal semicarbazone (FASC). The mathematical analysis was carried out with a recent computer program SIRKO which indicated the formation of one metal-ligand complex in each case and the logarithm of their stability constants are: log beta=2.02, 3.84, 4.58 and 4.52 for ligands FSC, MFSC, FASC and FPSC, respectively. A relation between stability and molecular weight of the ligands is proposed which may prove to be interesting as these complexes are being investigated for their cytotoxic activities.
Subject(s)
Copper , Cytotoxins/chemistry , Organometallic Compounds/chemistry , Semicarbazones , Drug Stability , Ethanol , Solutions , Spectrophotometry, UltravioletABSTRACT
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.
