Two series of novel and highly functionalised dispiropyrrolidines were synthesized using 1,3-dipolar cycloaddition reaction. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv using the Promega reagent BacTiter-Glo™ Microbial Cell Viability (BTG). Molecular docking analysis was carried out for the active compounds against the target enzyme enoyl-ACP reductase (InhA) to understand the possible binding mode. Of the 24 novel synthesized compounds, seven dispiropyrrolidines revealed inhibition with EC50 <25 μM. Compound 5b 7′-(4-chlorophenyl)-5′,6′,7′,7a'-tetrahydrodispiro[indan-2,5′-pyrrolo[1,2-c]-[1,3]thiazole-6′,2″-indan]-1,3,1″-trione was found to be the most active with EC50 of 10.52 μM, and was 2.2-fold more active than cycloserine. The docking result revealed that 5b had good affinity with the catalytic residues in InhA, forming hydrophobic and mild polar interactions with the important amino acids in the active site.
- 1,3-Dipolar cycloaddition
- Molecular docking