Orally active 1,2,4-trioxepanes: synthesis and antimalarial activity of a series of 7-arylvinyl-1,2,4-trioxepanes against multidrug-resistant Plasmodium yoelii in Swiss mice.
7-Arylvinyl-1,2,4-trioxepanes 7a-d, 8a-d, 9a-d, 10a-d, 11a-c, and 12a-c, prepared by photooxygenation of homoallylic alcohols 5a-d, were evaluated against multi-drug resistant Plasmodium yoelii nigeriensis in Swiss mice by oral and intramuscular routes. Trioxepane 11c, the most active compound of the series, showed more than 98% suppression of parsitaemia at 96 mg/kg by both oral and intramuscular routes. This is the first report on in vivo active 1,2,4-trioxepanes.
Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow, India. chandancdri@yahoo.com
Chandan
C
Singh
Shilpi
S
Pandey
Malvika
M
Sharma
Sunil K
SK
Puri
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010967:Plasmodium yoelii / Q000187:drug effects*; D020005:Propanols / Q000737:chemistry; D013329:Structure-Activity Relationship
D000962:Antimalarials; D006573:Heterocyclic Compounds, 1-Ring; D020005:Propanols; C006463:allyl alcohol