A critical evaluation of pyrrolo[2,3-d]pyrimidine-4-amines as Plasmodium falciparum apical membrane antigen 1 (AMA1) inhibitors
| Autor: | Christopher A. MacRaild, Damien R. Drew, Raymond S. Norton, Peter J. Scammells, San Sui Lim, Robin F. Anders, Indu R. Chandrashekaran, Raymond W. Lam, James G. Beeson, Shane M. Devine, Cael Debono, Martin J. Scanlon |
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| Rok vydání: | 2014 |
| Předmět: |
Pharmacology
Pyrimidine biology Improved solubility Organic Chemistry Pharmaceutical Science Plasmodium falciparum biology.organism_classification Biochemistry chemistry.chemical_compound Mechanism of action chemistry Drug Discovery medicine Molecular Medicine Parasite hosting medicine.symptom Apical membrane antigen 1 Function (biology) |
| Zdroj: | Med. Chem. Commun.. 5:1500-1506 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c4md00090k |
| Popis: | We have determined that a previously reported class of pyrrolo[2,3-d]pyrimidine-4-amines exhibit low binding to apical membrane antigen 1 (AMA1) and suffer from unattractive qualities, such as aggregation. We attempted to remove these traits by generating molecules with improved solubility, but this did not translate into enhanced binding affinity or inhibition of parasite growth in erythrocytes. These results indicate that anti-malarial activity is not primarily due to inhibition of AMA1 function, but mediated by an alternate or additional mechanism of action. |
| Databáze: | OpenAIRE |
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