Synthesis, characterization, and antitumor activity of a new iron-rifampicin complex: A novel prospective antitumor drug

Abstract

Rifampicin is a semi-synthetic derivative of rifamycin. It has a broad antibacterial activity. Iron is the most plentiful transition metal in human body. It is a crucial nutrient needed for numerous essential cellular functions. The present study is a trial to develop a novel antitumor candidate depending on formation of a complex between iron and rifampicin. After successful preparation, the resultant complex was characterized. Then its antitumor activity was investigated in vitro and in vivo. Comparison with the antitumor activity of pure rifampicin and cisplatin was also done. Compared to pure rifampicin (dose 0.107 mg/kg), iron-rifampicin complex was more potent in holding back the progression of the tumor. This was manifested by tumor mass shrinking, life span extension, and improvements in hematological portrait, liver and kidney functions, as well as antioxidant status. The complex mode of action may depend on its redox activity and/or induction of a mitochondrial apoptotic pathway. Regarding comparison with cisplatin, iron-rifampicin complex was a bit better antitumor. The complex administration to healthy mice displayed a non-toxic effect. Upon these, iron-rifampicin complex could be a promising addition in the upcoming generation of chemotherapeutics after more validation.