AI Article Synopsis
- Myristoyltransferase (NMT) is a promising target for malaria treatment due to its importance in the parasite's survival and the potential for small molecule inhibitors.
- Researchers simplified previous drug structures and identified a phenyl derivative, which allowed further modifications that produced a more effective pyridyl compound.
- The new pyridyl derivative demonstrated better potency against the NMT enzyme and malaria cells, with extremely low affinity levels and strong anti-plasmodial effects.
Article Abstract
-Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative , providing a versatile platform to study the effects of substitution on the scaffold, which yielded pyridyl . This molecule exhibited improved enzyme and cellular potency, and reduced lipophilicity compared to inhibitor . Further structure-based inhibitor design led to the discovery of , the most potent inhibitor in this series, which showed single-digit nM enzyme affinity and sub-μM anti-plasmodial activity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757856 | PMC |
| http://dx.doi.org/10.1039/c5md00242g | DOI Listing |
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Department of Chemistry , Imperial College London, London , SW7 2AZ , UK . Email: ; Tel: +44 (0)2075 943 752.
Article Synopsis
- Myristoyltransferase (NMT) is a promising target for malaria treatment due to its importance in the parasite's survival and the potential for small molecule inhibitors.
- Researchers simplified previous drug structures and identified a phenyl derivative, which allowed further modifications that produced a more effective pyridyl compound.
- The new pyridyl derivative demonstrated better potency against the NMT enzyme and malaria cells, with extremely low affinity levels and strong anti-plasmodial effects.
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