A novel dipeptide coupled with pyrazine-oxadiazole derivative as a potential antitubercular agent: Synthesis, radioiodination and bioevaluation

Tuberculosis (TB) is a disease caused by Mycobacterium and usually attack the lung. Synthesis of new dipeptide derivatives attached to antitubercular active heterocyclic rings like pyrazine and 1,3,4-oxadiazole called ethyl 2-(2-(5-((pyrazin-2-ylamino) methyl)-1,3,4-oxadiazol-2-ylthio) acetamido) acetamido)-3-(4-hydroxyphenyl) propanoate (EPOGTP) and iodinated EPOGTP are reported. The compounds have been characterized by mass, FT-IR and H-1 NMR spectroscopy. Their in vitro investigation against Mycobacterium tuberculosis cell line indicated good IC50 value of 210 mu g/ml for EPOGTP and 86 mu g/ml for iodo-EPOGTP. For study the biodisriution, the direct radioiodination of EPOGTP with iodine-131 using mild oxidizing agent, N-Bromosuccinimide (NBS), was performed and optimized for obtaining the maximum radiochemical purity (97.3 +/- 0.47%). Then, the in vivo biodistribution in healthy mice showed good accumulation of radioiodinated EPOGTP in lung of about 41.83 +/- 0.23% (the percentage of injected dose per gram of organ) at 15 min post-injection. As a conclusion, the synthetized dipeptide and its iodinated derivative could be further evaluated as a potential antitubercular agents.

Automated summary

Tuberculosis is a lung disease caused by Mycobacterium, and a study has reported the synthesis of new dipeptide derivatives attached to antitubercular active heterocyclic rings. These compounds showed promising antitubercular activity in vitro and in vivo, indicating their potential as tuberculosis treatment agents.