Antitumor Activity of Mesoionic Salts in Osteosarcoma

Among the bone tumors the Osteosarcoma (OS) is the most common in childhood and adolescence. For treatment there are few options of chemotherapeutic agents and the available ones cause side effects. The identification of new compounds with promising application in osteosarcoma is relevant to the treatment of this disease. The mesoionic salts belong to a class of heterocyclic compounds with antitumor activity that has been verified in different tumors such as melanoma and hepatocarcinoma. The present study aimed to evaluate the antitumor effect in vitro of mesoionic salts of 1,3,4-thiadiazolium-2-arylamine in osteosarcoma cells. The compounds were synthesized as shown in Scheme. By the MTT reduction assay, it was found that the MIC-F and MIC-NO2 salts reduced the relative viability of the MG-63 osteosarcoma cells, while the MI- 3,4F and MI-4F salts were not able to reduce the cell viability after treatment for 24 and 48 hours (Table). By counting cells with trypan blue, it was found that treatment with the MIC-NO2 and MIC-F salts, for 24 and 48 hours, reduced the viability of MG-63 cells and were therefore cytotoxic (Figure). The analysis of annexin-V and propidium iodide by flow cytometry revealed that treatment with MIC-NO2 and MIC-F induced cell death by apoptosis. Thus, among the four mesoionic salts evaluated in this study, only MIC-NO2 and MIC-F had cytotoxic effects on MG-63 osteosarcoma cells and, therefore, may be potential candidates for the development of drugs targeted to the treatment of this disease.