Identification and validation of the mode of action of the chalcone anti-mycobacterial compounds

B Anagani, J Singh, J P Bassin, G S Besra, C Benham, T R K Reddy, J A G Cox, M Goyal

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Objectives: The search for new TB drugs has become one of the great challenges for modern medicinal chemistry. An improvement in the outcomes of TB chemotherapy can be achieved by the development of new, shorter, cheap, safe and effective anti-TB regimens.

Methods: Chalcones (1a-1o) were synthesized and evaluated for their antimycobacterial activity against Mycobacterium bovis BCG using growth inhibition assays. Compound 1a was selected as a 'hit' compound. The mode of action of compound 1a, was identified by mycolic acid methyl esters (MAMEs) and fatty acid methyl esters (FAMEs) analysis using thin layer chromatography. Dose dependent experiments were conducted by over-expressing components of FAS-II in M. bovis BCG to confirm the target. Ligand binding using intrinsic tryptophan assay and molecular docking were used to further validate the target.

Results: MAMEs and FAMEs analysis showed dose-dependent reduction of MAMEs with the overall abundance of FAMEs suggesting that compound 1a targets mycolic acid biosynthesis. Direct binding of 1a to InhA was observed using an intrinsic tryptophan fluorescence binding assay, and a 2-fold IC50 shift was observed with an InhA overexpressing strain confirming InhA as the cellular target.

Conclusion: The chalcone 1a exhibits potent antimycobacterial activity, displays a good safety profile and is a direct inhibitor of InhA, a key component in mycolic acid synthesis, validating this series for further anti-TB drug development.

Original languageEnglish
Article number100041
Pages (from-to)100041
JournalThe Cell Surface
Publication statusPublished - Dec 2020

Bibliographical note

© 2020 Published by Elsevier B.V.


  • Chalcones
  • Docking
  • InhA
  • MIC
  • Mycolic Acids
  • Tuberculosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Microbiology
  • Applied Microbiology and Biotechnology


Dive into the research topics of 'Identification and validation of the mode of action of the chalcone anti-mycobacterial compounds'. Together they form a unique fingerprint.

Cite this