Fosfomycin analogues as potential antitumor agents

Fosfomycin represents a broad-spectrum antibiotic belonging to the class of phosphonic with a bactericidal activity against both gram-negative and some gram-positive microorganism. The aspect that makes it particularly interesting is the minimal occurrence of side effects which consist only of: rash, headache, nausea, rhinitis, vaginitis, etc. [1] In addition to bactericidal qualities, literature data report that several antibiotics, including Fosfomicyn, are possible inhibitors of DNA synthesis. This characteristic could lead them to become efficient antitumor agent. [2] Actually, a lot of study demonstrates that the co-administration of cis-platin (a well-known anticancer drug) and Fosfomycin is a good approach to decrease the onset of adverse effects due to the use of cis-platin alone such as ototoxicity and nephrotoxicity. [3] For the reasons abovementioned (overcoming cis-platin’s toxicity and verify if there’s the possibility to create innovative and safe anticancer drugs) the aim of our work was to synthetize fosfomycin’s derivatives. These analogues have been prepared with a simple and cheap one pot reaction using dimethylphosphonate and appropriate α-halo-ketones in the presence of sodium methoxide (CH3ONa) in methanol. However, in order to establish their potential antiproliferative activity against tumour cell lines and possible prevention toward non tumoral cells in vitro assays will be carried out.