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

• Published in: Natural product research Vol. 36; no. 15; pp. 3879 - 3886
• Main Authors: Puranik, Ninad V., Swami, Sagar, Misar, Ashwini V., Mamgain, Ritu, Gulawani, Swapnaja S., Sarkar, Srivastava, Pratibha
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.08.2022; Taylor & Francis Ltd
• Subjects: Analogs; and MMGBSA; Antibacterial activity; antimycobacterial activity; Computer applications; docking; Kinases; MD simulations; MMPBSA; Mycobacterium tuberculosis; Pantothenate kinase; Podocarflavone A synthesis; Screening; Tuberculosis; MD simulations; docking; antimycobacterial activity; Podocarflavone A synthesis; and MMGBSA; MMPBSA
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786419.2021.1893317

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 IC 50 values 21.82 µg/mL, 15.55 µg/mL, and 16.56 µg/mL, respectively. Compounds 8a, 8d, and 8e showed antibacterial activity with IC 50 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 IC 50 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.