New Adamantane-based Spiro 1,2,4-trioxanes Orally Effective Against Rodent and Simian Malaria.
From: Division of Medicinal and Process Chemistry and Division of Parasitology, Central Drug Research Institute, Lucknow-226001, India. chandancdri@yahoo.com
Journal of medicinal chemistry
- Publish Date: Feb 2007
- ISSN: 0022-2623
- Volume: 50
- Issue: 3
- Pages: 521-7
- Medium: Print
- Language: English
- Citation (JAMA): Singh Chandan, Kanchan Rani, Sharma Upasana, et al. New Adamantane-based Spiro 1,2,4-trioxanes Orally Effective Against Rodent and Simian Malaria.. J. Med. Chem. Feb 2007;50:521-7
Abstract
New 6-arylvinyl- and 6-adamantylvinyl-substituted 1,2,4-trioxanes (13a-g and 14a,b) have been prepared and evaluated for antimalarial activity against multidrug resistant Plasmodium yoelii nigeriensis in mice by both oral and intramuscular routes. While all the 6-arylvinyl-substituted trioxanes, 13a-f, showed promising activity, none of the 6-adamantylvinyl-substituted trioxanes, 13g and 14a,b, exhibited significant activity. Trioxane, 13f, the most active compound of the series, provided 100% and 80% protection to malaria-infected mice at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively, by oral route. In this model, beta-arteether (3) provided 100% protection at 48 mg/kg x 4 days and only 20% protection at 24 mg/kg x 4 days. Trioxane 13f also showed complete suppression of parasitaemia at 10 mg/kg x 4 days by oral route in rhesus monkeys infected with P. cynomolgi. None of these trioxanes, except 13f, showed significant activity by the intramuscular route.
Mesh Headings (Keywords): Adamantane, Administration, Oral, Animals, Antimalarials, Drug Resistance, Heterocyclic Compounds, 1-Ring, Injections, Intramuscular, Macaca mulatta, Malaria, Mice, Parasitemia, Plasmodium cynomolgi, Plasmodium yoelii, Spiro Compounds, Structure-Activity Relationship
Check for Full Text / PubMed Unique Identifier (PMID): 17266204
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