The first synthesis of podocarflavone A and its analogs and evaluation of their antimycobacterial potential against Mycobacterium tuberculosis with the support of virtual screening

The first synthetic route developed for Podocarflavone A reported from Podocarpus macrophyllus and its analogs in 7 steps. Computational analysis for binding with the pantothenate kinase (3AVO) of Mycobacterium tuberculosis showed their docking score (ds) in the range of -8.9 to -9.3 Kcal/mol. MD simulations delineated the stability of the protein-ligand complexes in the TIP3P model. MMGBSA and MMPBSA values of 8d were -42.46 Kcal/mol and -14.58 Kcal/mol, respectively. Further in-vitro antitubercular screening of compounds 8a, 8d, and 8e against M. tuberculosis H37Ra using XRMA protocol exhibited promising antimycobacterial activity with IC50 values 21.82 µg/mL, 15.55 µg/mL, and 16.56 µg/mL, respectively. Compounds 8a, 8d, and 8e showed antibacterial activity with IC50 values 41.56 µg/mL, 24.72 µg/mL, and 72.45 µg/mL respectively against the Staphylococcus aureus. 8a and 8d showed inhibition with IC50 values 39.6 µg/mL and 27.64 µg/mL, respectively, against Bacillus subtilis. The present study could help in the further development of lead molecules against tuberculosis.