Novel bis- and tris-1,2,4-trioxanes: synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice.
A new series of bis-1,2,4-trioxanes 12a-h, 13a-h, and 14a-h and tris-1,2,4-trioxanes 12i-14i were prepared and evaluated against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. Cyclopentane-based bis-trioxanes 12a, 12b, 12f-h and cyclohexane-based bis-trioxanes 13a, 13f, and 13g showed promising activity. All the tris-1,2,4-trioxanes were found to be inactive. Bis-trioxane 12a, the most active compound of the series, provided 100% and 80% protection to infected mice at 48 and 24 mg/kg x 4 days, respectively. Clinically useful drug beta-arteether provided 100% and 20% protection at similar doses.
Singh
Chandan
C
Division of Medicinal and Process Chemistry and Division of Parasitology, Central Drug Research Institute, Lucknow-226001, India. chandancdri@yahoo.com
Verma
Ved Prakash
VP
Naikade
Niraj Krishna
NK
Singh
Ajit Shankar
AS
Hassam
Mohammad
M
Puri
Sunil K
SK
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D010273:Parasitic Diseases, Animal / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010967:Plasmodium yoelii / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds