Development of a new anti-TB drug

Tuberculosis remains one of the leading causes of death worldwide. Almost a third of the world's population is infected with a pathogen; about 8 million people develop active TB each year, resulting in the death of 2 million people. The therapeutic regimens currently used against tuberculosis, developed in the 1970s, are difficult to tolerate by patients and require the appointment of a combination of several anti-tuberculosis drugs for at least 6 months. The situation is exacerbated by the emergence of multiple resistant tuberculosis and an extremely unfavorable combination of tuberculosis and HIV / AIDS. Today there is an acute shortage of new anti-tuberculosis drugs.

Japanese scientists report the development of OPC-67683, a derivative of nitro-dihydro-imidazooxazole, which may solve the problem of the acute shortage of anti-TB drugs. The substance is an inhibitor of mycolic acid biosynthesis, has no mutagenic properties and is very active against Mycobacterium tuberculosis, including multidrug-resistant strains, which is confirmed by in vitro with an exceptionally low minimum inhibitory concentration (MIC) - 0.006-0.024 mcg / ml and in vivo high therapeutic efficacy at low doses. In addition, a study of the postantibiotic effect of OPC-67683 showed that the drug has a high and dose-dependent activity compared to M. tuberculosis H37Rv located intracellularly after a peak of exposure. 4 hours. The activity of OPC-67683 at a concentration of 0.1 μg / ml was similar to the activity of the first-line drug, rifampicin, at a concentration of 3 μg / ml.

The combination of OPC-67683 with rifampicin and pyrazinamide has demonstrated the possibility of significantly faster eradication of viable M. tuberculosis from the lungs compared to standard therapy including rifampicin, isoniazid , ethambutol and pyrazinamide. In addition, OPC-67683 is not metabolized and does not affect the activity of hepatic microsomal enzymes, which makes it possible to combine OPC-67683 with other drugs, including antiretrovirals that induce cytochrome P450 or are metabolized by this enzyme.

Thus, given the unique properties of OPC-67683, this substance is a promising anti-tuberculosis drug that can solve the problems of treating tuberculosis.