Quinoxaline 1,4-di-N-oxide Derivatives as New Antinocardial Agents

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the "mycetoma belt" including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-<i>N</i>-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from <i>N. brasiliensis</i>, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-<i>N</i>-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (<b>N-05</b>, <b>N-09</b>, <b>N-11</b>, and <b>N-13</b>) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-<i>N</i>-oxide could be used to develop new and more potent antinocardial agents.