OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice

摘要: Background Tuberculosis (TB) is still a leading cause of death worldwide. Almost third the world's population infected with TB bacilli, and each year approximately 8 million people develop active 2 die as result. Today's treatment, which dates back to 1970s, long burdensome, requiring at least 6 mo multidrug chemotherapy. The situation further compounded by emergence multidrug-resistant (MDR-TB) infection's lethal synergy HIV/AIDS. Global health philanthropic organizations are now pleading for new drug interventions that can address these unmet needs in treatment. Methods Findings Here we report OPC-67683, nitro-dihydro-imidazooxazole derivative was screened help combat treatment. compound mycolic acid biosynthesis inhibitor found be free mutagenicity possess highly potent activity against TB, including MDR-TB, shown its exceptionally low minimum inhibitory concentration (MIC) range 0.006–0.024 μg/ml vitro effective therapeutic doses vivo. Additionally, results post-antibiotic effect OPC-67683 on intracellular Mycobacterium tuberculosis showed agent dose-dependently also M. H37Rv after 4-h pulsed exposure, this 0.1 similar first-line rifampicin (RFP) 3 μg/ml. combination RFP pyrazinamide (PZA) exhibited remarkably quicker eradication (by mo) viable bacilli lung comparison standard regimen consisting RFP, isoniazid (INH), ethambutol (EB), PZA. Furthermore, not affected nor did it affect liver microsome enzymes, suggesting possibility used drugs, anti-retrovirals, induce or metabolized cytochrome P450 enzymes. Conclusions We concluded based properties has potential