title: Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents.
abstract: A series of 4-oxycoumarin derivatives was synthesized, characterized and evaluated in vitro and in vivo for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied showed potent in vitro activity with low IC50 values in the micro molar (μM) range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae, respectively. Compounds 8 and 9 were identified to be the most promising antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range. The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94 nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds also displayed promising adulticidal activity (74.9 ± 4.8% and 69.4 ± 2.8%, respectively) in the primary rodent (jird) screen. This study also serves as a starting point for investigating structure-activity relationship with different amino substituents.
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, BS 10/1, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Sweta
authors.initials: S
authors.lastname: Misra
authors.affiliation: Department of Chemistry, MMV, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Lav Kumar
authors.initials: LK
authors.lastname: Singh
authors.affiliation: Department of Chemistry, MMV, Banaras Hindu University, Varanasi 221005, India.
authors.lastname: Priyanka
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, BS 10/1, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Gupta
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, BS 10/1, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: shailja_bhattacharya@cdri.res.in.
authors.forename: Shailja
authors.initials: S
authors.lastname: Misra-Bhattacharya
authors.affiliation: Department of Chemistry, MMV, Banaras Hindu University, Varanasi 221005, India. Electronic address: dikshakatiyar@gmail.com.
authors.forename: Diksha
authors.initials: D
authors.lastname: Katiyar
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000187:drug effects*; D060326:Chemistry Techniques, Synthetic; D003374:Coumarins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005368:Filariasis / Q000188:drug therapy; D005369:Filaricides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005849:Gerbillinae; D020128:Inhibitory Concentration 50; D008297:Male
chemical_list: D003374:Coumarins; D005369:Filaricides
keywords: Antifilarial; Brugia malayi; Coumarins; jird; β-amino alcohol