Spiro Benzodiazepine Substituted Fluorocoumarins as Potent Anti-Anxiety Agents
Dayanand N. Patagar, Akshay Uttarkar, Swarna M. Patra, Jagadish H. Patil, Raviraj Kusanur, Vidya Niranjan, H. G. Ashok Kumar
Abstract
1,5-Benzodiazepines are one of the important class of tranquilizers. The fusion of heterocyclic systems like coumarins and indolines with the benzodiazepine seems quite encouraging for the synthesis of derivatives with enhanced anti-anxiety property. The benzodiazepine derivatives containing fluorine were synthesized and studied for their anti-anxiety activity on mice using plus maze apparatus with sodium pentabarbitone as the standard. Compound with mono substituted fluorine showed comparable anti-anxiety activity with the standard. The docking studies with Translocator protein (TSPO) (PDB: 4UC2) were done and further supported by molecular dynamics simulations. The in vivo test results are in well agreement with docking and molecular dynamics simulation studies.