Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents
| Autor: | Kumkum Srivastava, Surendra Puri, S. Raja Kumar, Prem M. S. Chauhan, Ashok Kumar |
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| Rok vydání: | 2009 |
| Předmět: |
Amsacrine
Stereochemistry Plasmodium falciparum Clinical Biochemistry Cyanuric chloride Pharmaceutical Science Biochemistry Chemical synthesis Antimalarials Mice chemistry.chemical_compound Drug Discovery Animals Potency Antimalarial Agent Molecular Biology chemistry.chemical_classification biology Triazines Organic Chemistry Aromatic amine biology.organism_classification chemistry Acridine Molecular Medicine Plasmodium yoelii Nuclear chemistry |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:6996-6999 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2009.10.010 |
| Popis: | There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malaria after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride. The series of new hybrid 9-anilinoacridine triazines were evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of Plasmodium falciparum and their cytotoxicity were determined on VERO cell line. Of the evaluated compounds, two compounds 17 (IC(50)=4.21 nM) and 22 (IC(50)=4.27 nM) displayed two times higher potency than CQ (IC(50)=8.15 nM). Most of the compounds showed fairly high selectivity index. The compounds 13 and 29 displayed >96.59% and 98.73% suppression, respectively, orally against N-67 strain of Plasmodium yoelii in swiss mice at dose 100 mg/kg for four days. |
| Databáze: | OpenAIRE |
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