Source:http://linkedlifedata.com/resource/pubmed/id/19105653
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-1-23
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| pubmed:abstractText |
A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride (1) was isolated from Prosopis glandulosa var. glandulosa. Three additional new (2-4) and one known (5) indolizidines were also isolated, and the dihydrochloride salts of 1-3 (compounds 6, 7, and 8) were prepared. Structures were determined by 1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal activity against Cryptococcus neoformans and Aspergillus fumigatus (IC(50) values = 0.4 and 3.0 microg/mL, respectively) and antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare (IC(50) values of 0.35 and 0.9 microg/mL, respectively). The remarkable in vitro fungicidal activity of 1-4 against C. neoformans (MFCs = 0.63-1.25 microg/mL) and 2, 3, and 5 against A. fumigatus (MFCs = 0.63-2.5 microg/mL) were similar to amphotericin B, but >2-4-fold more potent than 6-8. Prosopilosidine (1) showed potent in vivo activity at 0.0625 mg/kg/day/ip for 5 days in a murine model of cryptococcosis by eliminating approximately 76% of C. neoformans infection from brain tissue compared to approximately 83% with amphotericin B at 1.5 mg/kg/day. Compounds 1 and 4 exhibited potent activity and high selectivity index (SI) values against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum, with IC(50) values of 39 and 95 ng/mL and 42 and 120 ng/mL, respectively (chloroquine, IC(50) = 17 and 140 ng/mL). Prosopilosine (1) also showed in vivo antimalarial activity, with an ED(50) value of approximately 2 mg/kg/day/ip against Plasmodium berghei-infected mice after 3 days of treatment.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1520-6025
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
72
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
92-8
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| pubmed:meshHeading |
pubmed-meshheading:19105653-Animals,
pubmed-meshheading:19105653-Anti-Infective Agents,
pubmed-meshheading:19105653-Antiparasitic Agents,
pubmed-meshheading:19105653-Aspergillus fumigatus,
pubmed-meshheading:19105653-Brain,
pubmed-meshheading:19105653-Candida albicans,
pubmed-meshheading:19105653-Chloroquine,
pubmed-meshheading:19105653-Cryptococcus neoformans,
pubmed-meshheading:19105653-Disease Models, Animal,
pubmed-meshheading:19105653-Drug Screening Assays, Antitumor,
pubmed-meshheading:19105653-Humans,
pubmed-meshheading:19105653-Indolizidines,
pubmed-meshheading:19105653-Inhibitory Concentration 50,
pubmed-meshheading:19105653-Methicillin-Resistant Staphylococcus aureus,
pubmed-meshheading:19105653-Mice,
pubmed-meshheading:19105653-Microbial Sensitivity Tests,
pubmed-meshheading:19105653-Molecular Structure,
pubmed-meshheading:19105653-Nevada,
pubmed-meshheading:19105653-Plants, Medicinal,
pubmed-meshheading:19105653-Plasmodium berghei,
pubmed-meshheading:19105653-Prosopis
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| pubmed:year |
2009
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| pubmed:articleTitle |
Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa var. glandulosa.
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| pubmed:affiliation |
National Center for Natural Products Research and Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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