title: Antifilarial activity of 1,3-diarylpropen-1-one: effect on glutathione-S-transferase, a phase II detoxification enzyme.
abstract: Chalcone derivatives were evaluated for their antifilarial activity on Setaria cervi using glutathione-S-transferase (GST) as a drug target. The compounds 1-(4-benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4-methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) showed a significant suppression (P < 0.01) in GST activity of adult female parasite extract at 3 microM concentration in vitro. However, GST activity was detected along with depletion in GSH level. Except Compounds 1 and 2, all exhibited a significant effect on the motility and viability of adult parasites. Compounds 3-(4-chlorophenyl)-1-(4-piperidin-1-yl-phenyl)prop-2-en-1-one (3), 1-(4-benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4-methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) exhibited major irreversible effects on viability and resulted in parasite death and also inhibited the GST activity by 84-100% in vitro. We report for the first time the antifilarial activity of chalcones on GST of adult parasites. This study also strengthens our previous findings where GST is reported as a potential drug target for antifilarials.
authors.affiliation: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi, India. skawasthi@chemistry.du.ac.in
authors.forename: Satish K
authors.initials: SK
authors.lastname: Awasthi
authors.forename: Nidhi
authors.initials: N
authors.lastname: Mishra
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Dixit
authors.forename: Alka
authors.initials: A
authors.lastname: Singh
authors.forename: Marshleen
authors.initials: M
authors.lastname: Yadav
authors.forename: Sudhanshu S
authors.initials: SS
authors.lastname: Yadav
authors.forename: Sushma
authors.initials: S
authors.lastname: Rathaur
mesh_terms: D000818:Animals; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005369:Filaricides / Q000737:chemistry / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D017182:Setaria Nematode / Q000187:drug effects* / Q000201:enzymology
chemical_list: D047188:Chalcones; D005369:Filaricides; D005982:Glutathione Transferase; D011407:Propane