Synthesis, Characterization and Biological Evaluation of Novel 1, 4-Benzodiazepine Derivatives as Potent Anti-Tubercular Agents

Background: Benzodiazepines are interesting compounds due to their therapeutic properties. TB chemotherapy is highly regulated and Its research research is often considered non-remunerative. Hence, there remains a pressing requisite to discover novel, potent and safe anti-TB agents. Objective: One of the biggest problem of Tuberculosis is the lack of effective treatments. Bedaquiline (2013) and Delaminid (2014) are the only two agents approved for treating tuberculosis after Rifampicin (1963). This clearly shows the need for new lead molecules to fight against tuberculosis. Methodology: In the present work, a series of eighteen derivatives of 1, 4-Benzodiazepines were synthesized by condensation of o-phenylenediamines with 1, 3-diketone (Dimedone). Further these synthesized derivatives were analyzed by IR, NMR and MASS spectral studies and are screened for anti-tubercular and antimicrobial activity. Results: Among these, potent activity were observed for compounds 9, 10 (MIC 1.6 μg/mL) followed by 11(3.12 μg/mL), 04 (6.25 μg/mL) against M. tuberculosis H37Rv. We report here the synthesis, screening data and SAR studies of Benzodiazepines and its derivatives as Antitubercular agents. Conclusion: In conclusion, we synthesized eighteen 1, 4-Benzodiazepines derivatives with selective anti-tubercular activity.

Key message: We report here a new method for the preparation of some novel 1, 4-benzodiazepine derivatives with selective anti TB activity.