Design, synthesis and biological evaluation of phenanthridine amide and 1,2,3-triazole analogues against Mycobacterium tuberculosis.
RSC Med Chem
; 14(8): 1549-1561, 2023 Aug 16.
Article
in En
| MEDLINE
| ID: mdl-37593576
ABSTRACT
The phenanthridine core exhibits antitubercular activity, according to reports from the literature. Several 1,2,3-triazole-based heterocyclic compounds are well-known antitubercular agents. A series of twenty-five phenanthridine amide and 1,2,3-triazole derivatives are synthesized and analyzed using ESI-MS, 1HNMR, and 13CNMR on the basis of our earlier findings that phenanthridine and 1,2,3-triazoles shown good antitubercular activity. The synthesized phenanthridine amide and 1,2,3-triazole analogues were tested in vitro against Mycobacterium tuberculosis H37Rv and minimum inhibitory concentration (MIC) values were determined utilizing non-replicating and replicating low-oxygen recovery assay (LORA) and microplate Alamar Blue assay (MABA) methodologies. The phenanthridine amide derivative PA-01 had an MIC of 61.31 µM in MABA and 62.09 µM in the LORA technique, showing intense anti-TB activity. Amongst the phenanthridine triazole derivatives, PT-09, with MICs of 41.47 and 78.75 µM against the tested strain of Mtb in both MABA and LORA was the most active one. The final analogues' drug-likeness is predicted using absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies. The most active compounds PA-01 and PT-09 were further subjected to in silico docking studies. Using the Glide module of Schrodinger, molecular docking analysis was carried out to estimate the plausible binding pattern of PA-01 and PT-09 at the active site of Mycobacterial DNA topoisomerase II (PDB code 5BS8). Further, molecular dynamics studies of PA-01 and PT-09 were also carried out.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
RSC Med Chem
Year:
2023
Document type:
Article