Design, synthesis and biological evaluation of aryl pyrimidine derivatives as potential leishmanicidal agents
| Autor: | Avinash Tiwari, Susmita Pandey, S.N. Suryawanshi, Suman Gupta, Rahul Shivahare, Santosh Kumar |
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| Rok vydání: | 2013 |
| Předmět: |
Pyrimidine
Sodium stibogluconate Clinical Biochemistry Leishmania donovani Antiprotozoal Agents Pharmaceutical Science Pharmacology Biochemistry chemistry.chemical_compound Structure-Activity Relationship Parasitic Sensitivity Tests In vivo parasitic diseases Drug Discovery medicine Structure–activity relationship Amastigote Molecular Biology Miltefosine biology Dose-Response Relationship Drug Molecular Structure Chemistry Aryl Organic Chemistry biology.organism_classification Pyrimidines Drug Design Molecular Medicine medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 23(18) |
| ISSN: | 1464-3405 |
| Popis: | A series of substituted aryl pyrimidine derivatives was synthesized and evaluated in vitro for their antileishmanial potential against intracellular amastigotes of Leishmania donovani using reporter gene luciferase assay. Among all, 8 compounds showed promising IC50 values ranging from 0.5 to 12.9 μM. Selectivity indices (S.I.) of all these compounds are far better than reference drugs, sodium stibogluconate (SSG) and miltefosine. On the basis of good S.I., compounds were further screened for their in vivo antileishmanial activity against L. donovani/hamster model. Compounds 2d, 4a and 4b have shown significant inhibition of parasitic multiplication that is 88.4%, 78.1% and 78.2%, respectively at a daily dose of 50 mg/kg × 5 days, when administered intraperitoneally. Compound 2d is most promising one, which may provide a new lead that could be exploited as a new antileishmanial agent. |
| Databáze: | OpenAIRE |
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