Synthesis and antimalarial activity of pyrazolo and pyrimido benzothiazine dioxide derivatives
| Autor: | Neira Gamboa, Angel Alvarez-Larena, Mario V. Capparelli, Simón E. López, Arthur Barazarte, Jaime Charris, Juan Rodrigues, Gricela Lobo |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Pharmacology Magnetic Resonance Spectroscopy Spectrophotometry Infrared Pyrimidine biology Plasmodium berghei Stereochemistry Chemical structure Organic Chemistry Thiazines Biological activity General Medicine Benzothiazine biology.organism_classification Chemical synthesis Antimalarials chemistry.chemical_compound chemistry In vivo Drug Discovery Animals Hemoglobin |
| Zdroj: | European Journal of Medicinal Chemistry. 44:1303-1310 |
| ISSN: | 0223-5234 |
| Popis: | A series of phenylsubstituted pyrazolo and pyrimido benzothiazine dioxide derivatives were synthesized and investigated for their abilities to inhibit beta-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent Plasmodium berghei. Compounds 3-amino-7-chloro-9-(2'-methylphenyl)-1,9-dihydro-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide 2b and 2,4-diamino-8-chloro-10H-phenyl-pyrimido-[5,4-b]benzothiazine 5,5-dioxide 3a were the most promising as inhibitors of hemoglobin hydrolysis, however, their effect as inhibitors of beta-hematin formation was marginal, except for compound 3-amino-7-chloro-9-(3'-chlorophenyl)-1,9dihydro-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide 2g. The most active compound to emerge from the in vitro and in vivo murine studies was 2b, suggesting an antimalarial activity via inhibition of hemoglobin hydrolysis, however, not as efficient as chloroquine. |
| Databáze: | OpenAIRE |
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