ABSTRACT
BACKGROUND:Previous research indicated that iron-fluorouracil-phenanthroline complex has good antitumor activity in vitro, which can inhibit the proliferation of human cancer cels. OBJECTIVE:To detect the antitumor activity and toxicity of iron-fluouracil-phenanthroline complex, [Fe(5-Fu)2(Phen)SO4],in vivo. METHODS:A total of 40 Kunming mice were randomly divided into four groups, which were intraperitoneally injected with 72, 102.9, 147, 210 mg/kg [Fe(5-Fu)2(Phen)SO4] and the half lethal dose of the complex was detected. One day after the establishment of mouse S180 sarcoma models, the model mice were randomly divided into eight groups, and administered with the intraperitoneal injection of 15 mg/kg (low dose group), 30 mg/kg (middle dose group), 60 mg/kg (high dose group) [Fe(5-Fu)2(Phen)SO4], normal saline (negative control group), cisplatin (positive control group), 5-fluorouracil, iron-salt and phenanthroline, respectively. The injection was done once a day, lasting for 7 days. The weight of sarcomas, body weight, the main organ coefficient and histopathological changes of the main organs were detected. RESULTS AND CONCLUSION: The half lethal dose of [Fe(5-Fu)2(Phen)SO4] was 103.9 mg/kg. Compared with the negative control group, high dose group, positive control group and 5-fluorouracil could significantly inhibit the growth of the tumor (P< 0.05 orP< 0.01), and the effect of high dose group was the most obvious (P < 0.01). Compared with cisplatin, 60mg/kg [Fe(5-Fu)2(Phen)SO4] had a weaker inhibitory effect on the kidney, but higher inhibitory effect on the liver, spleen and thymus, indicating the complex has a lower nephrotoxicity, but stronger immunotoxicity and hepatotoxicity than cisplatin.
ABSTRACT
BACKGROUND:Anticancer drug and organic metal complexes wil form a new structure or a change in ion concentration, thus changing both the activity and toxicity to produce a synergistic effect. OBJECTIVE:To synthesize new high-efficient and low-toxic metal-fluorouracil complexes as anticancer drugs. METHODS:Copper, zinc and iron salts and fluorouracil were used to synthesize four copper, zinc and iron-fluorouracil complexes that were [Cu(5-Fu)2Cl2], [Cu(5-Fu)2(NO3)2], [Fe(5-Fu)3]SO4 and [Zn(5-Fu)2Cl2]. Preliminary chemical structures of the four complexes were confirmed by elemental analysis and mass spectrometry. Their inhibitory activity on human cancer cells, human leukemia cellline K562 and human colon cancer cellline HCT-116, was measured by MTT colorimetric assay. RESULTS AND CONCLUSION:[Cu(5-Fu)2Cl2], [Cu(5-Fu)2(NO3)2], [Zn(5-Fu)2Cl2] and [Fe(5-Fu)3SO4] were successful y synthesized. These four complexes at a mass concentration of 0.1-100 mg/L inhibited the proliferation of K562 and HCT-116 to different extents. The IC 50 values of these four complexes on K562 and HCT-116 cells were lower than those of fluorouracil, and their cytotoxicity was 1.5-7.8 times higher than that of fluorouracil. To conclude, copper/iron/zinc-fluorouracil complexes exhibit synergic inhibitory effects on cancer cellproliferation.