Michael Adduct of Sulfonamide Chalcone Targets Folate Metabolism in Brugia Malayi Parasite

Priyanka S. Bhoj, Sandeep P. Bahekar, Shambhavi Chowdhary, Namdev S. Togre, Nitin P. Amdare, Lingaraj Jena, Kalyan Goswami, Hemant Chandak

Research output: Contribution to journalArticlepeer-review


A series of Michael adducts of malononitrile and sulfonamide chalcones were synthesized, characterized, and evaluated for their antifilarial activity. Out of 14 compounds, N-(4-(4,4-dicyano-3-p-tolylbutanoyl)phenyl)benzenesulfonamide showed favorable drug-likeness properties with marked antifilarial effects at micro-molar dosages. Apoptosis in Brugia malayi microfilariae was confirmed by EB/AO staining, MTT assay, and cytoplasmic cytochrome c ELISA. Since chalcone and folate synthesis pathways share the same substrate, we hypothesize a structural analogy-based inhibition of folate metabolism by this compound. Molecular docking against a pre-validated BmDHFR protein showed more favorable thermodynamic parameters than a positive control, epicatechin-3-gallate. The compound significantly suppressed the DHFR activity in a parasite extract in vitro. Our hypothesis is also supported by a significant reversal of DHFR inhibition by folate addition, which indicated a plausible mechanism of competitive inhibition. These results demonstrate that targeting filarial folate metabolism through DHFR with consequent apoptosis induction might be rewarding for therapeutic intervention. This study reveals a novel rationale of the structural analogy-based competitive inhibition of DHFR by Michael adducts of sulfonamide chalcones.

Original languageEnglish (US)
Article number723
Issue number3
StatePublished - Mar 2023
Externally publishedYes


  • Michael adducts
  • antifilarial
  • dihydrofolate reductase
  • folate metabolism
  • sulfonamide chalcone

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Michael Adduct of Sulfonamide Chalcone Targets Folate Metabolism in Brugia Malayi Parasite'. Together they form a unique fingerprint.

Cite this