Structure-activity relationships reveal beneficial selectivity profiles of inhibitors targeting acetylcholinesterase of disease-transmitting mosquitoes
| العنوان: | Structure-activity relationships reveal beneficial selectivity profiles of inhibitors targeting acetylcholinesterase of disease-transmitting mosquitoes |
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| المؤلفون: | Vidal-Albalat, Andreu, Kindahl, Tomas, 1980, Rajeshwari, Rajeshwari, Lindgren, Cecilia, Forsgren, Nina, Kitur, Stanley, Tengo, Laura Sela, Ekström, Fredrik, Kamau, Luna, Linusson, Anna, 1970 |
| المصدر: | Journal of Medicinal Chemistry. 66(9):6333-6353 |
| الوصف: | Insecticide resistance jeopardizes the prevention of infectious diseases such as malaria and dengue fever by vector control of disease-transmitting mosquitoes. Effective new insecticidal compounds with minimal adverse effects on humans and the environment are therefore urgently needed. Here, we explore noncovalent inhibitors of the well-validated insecticidal target acetylcholinesterase (AChE) based on a 4-thiazolidinone scaffold. The 4-thiazolidinones inhibit AChE1 from the mosquitoes Anopheles gambiae and Aedes aegypti at low micromolar concentrations. Their selectivity depends primarily on the substitution pattern of the phenyl ring; halogen substituents have complex effects. The compounds also feature a pendant aliphatic amine that was important for activity; little variation of this group is tolerated. Molecular docking studies suggested that the tight selectivity profiles of these compounds are due to competition between two binding sites. Three 4-thiazolidinones tested for in vivo insecticidal activity had similar effects on disease-transmitting mosquitoes despite a 10-fold difference in their in vitro activity. |
| وصف الملف: | electronic |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-208264 https://doi.org/10.1021/acs.jmedchem.3c00234 https://umu.diva-portal.org/smash/get/diva2:1758890/FULLTEXT01.pdf |
| قاعدة البيانات: | SwePub |
Find this issue from the American Chemical Society | تدمد: | 00222623 |
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| DOI: | 10.1021/acs.jmedchem.3c00234 |