Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas
| Autor: | Christian Wolf, Jayakumar K. Natarajan, Kimberly Yearick, Daniel P. Iwaniuk, Kekeli Ekoue-Kovi, Angel C. de Dios, Paul D. Roepe, John N. Alumasa |
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| Rok vydání: | 2009 |
| Předmět: |
Stereochemistry
Plasmodium falciparum Clinical Biochemistry Drug Resistance Pharmaceutical Science Drug resistance Biochemistry Article Antimalarials Inhibitory Concentration 50 chemistry.chemical_compound Chloroquine Drug Discovery Side chain medicine Animals Urea Potency Moiety Molecular Biology chemistry.chemical_classification Sulfonamides biology Chemistry Organic Chemistry Thiourea biology.organism_classification Amides Sulfonamide Molecular Medicine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:270-283 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2008.11.009 |
| Popis: | We report the synthesis and in vitro antimalarial activities of more than 50 7-chloro-4-aminoquinolyl-derived sulfonamides 3 – 8 and 11 – 26 , ureas 19 – 22 , thioureas 23 – 26 , and amides 27 – 54 . Many of the CQ analogues prepared for this study showed submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strains of Plasmodium falciparum ) and low resistance indices were obtained in most cases. Systematic variation of the side chain length and introduction of fluorinated aliphatic and aromatic termini revealed promising leads that overcome CQ resistance. In particular, sulfonamide 3 exhibiting a short side chain with a terminal dansyl moiety combined high antiplasmodial potency with a low resistance index and showed IC 50 s of 17.5 and 22.7 nM against HB3 and Dd2 parasites. |
| Databáze: | OpenAIRE |
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