Orally active 1,2,4-trioxanes: synthesis and antimalarial assessment of a new series of 9-functionalized 3-(1-arylvinyl)-1,2,5-trioxaspiro[5.5]undecanes against multi-drug-resistant plasmodium yoelii nigeriensis in mice.
Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days by oral route. Trioxanes 10, 12, 14, 16, 18, 20, and 22 have shown promising antimalarial activity. Trioxanes 14 and 18, the two most active compounds of the series, provide 100% and 60% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively. In this model beta-arteether provides 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively.
Singh
Chandan
C
Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow-226001, India. chandancdri@yahoo.com
Malik
Heetika
H
Puri
Sunil K
SK
D000284:Administration, Oral; D000586:Amination; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D015394:Molecular Structure; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D015996:Survival Rate
C503429:1,2,4-trioxane; D000962:Antimalarials; D037621:Artemisinins; D006571:Heterocyclic Compounds