Adinarayana Nandikolla, Yogesh Mahadu Khetmalis, Boddupalli Venkata Siva Kumar, Ala Chandu, Banoth Karan Kumar, Gauri Shetye, Rui Ma, Sankaranarayanan Murugesan, Scott G Franzblau, Kondapalli Venkata Gowri Chandra Sekhar
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, HNMR, and CNMR 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 against 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 ��M in MABA and 62.09 ��M in the LORA technique, showing intense anti-TB activity. Amongst the phenanthridine triazole derivatives, PT-09, with MICs of 41.47 and 78.75 ��M 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 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 DNA topoisomerase II (PDB code: ). Further, molecular dynamics studies of PA-01 and PT-09 were also carried out.
