title: Synthesis and antimalarial activity of 3,3-spiroanellated 5,6-disubstituted 1,2,4-trioxanes.
abstract: Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. The most active compound of the series (compound 25) provided 100% protection at 24 mg/kg × 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. In this model, β-arteether provided 100 and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively, by oral route. Compound 25 displayed a similar in vitro pharmacokinetic profile to that of reference drug β-arteether. The activity results demonstrated the importance of an aryl moiety at the C-5 position on the 1,2,4-trioxane pharmacophore.
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Ranjani
authors.initials: R
authors.lastname: Maurya
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Awakash
authors.initials: A
authors.lastname: Soni
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Devireddy
authors.initials: D
authors.lastname: Anand
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Makthala
authors.initials: M
authors.lastname: Ravi
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Kanumuri S R
authors.initials: KS
authors.lastname: Raju
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Isha
authors.initials: I
authors.lastname: Taneja
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Niraj K
authors.initials: NK
authors.lastname: Naikade
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.lastname: Wahajuddin
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kanojiya
authors.affiliation: Division of Medicinal & Process Chemistry, Division of Parasitology, Division of Pharmacokinetics and Metabolism, and Sophisticated Analytical Instrument Facility, Central Drug Research Institute , Lucknow-226001, India.
authors.forename: Prem P
authors.initials: PP
authors.lastname: Yadav
keywords: 1,2,4-trioxane; antimalarial; in vivo; orally active