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QSAR and Pharmacophore Modeling of Nitrogen Heterocycles as Potent Human N-Myristoyltransferase (Hs-NMT) Inhibitors
- Source :
- Molecules, Molecules, Vol 26, Iss 1834, p 1834 (2021), Volume 26, Issue 7
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- N-myristoyltransferase (NMT) is an important eukaryotic monomeric enzyme which has emerged as an attractive target for developing a drug for cancer, leishmaniasis, ischemia-reperfusion injury, malaria, inflammation, etc. In the present work, statistically robust machine leaning models (QSAR (Quantitative Structure–Activity Relationship) approach) for Human NMT (Hs-NMT) inhibitory has been performed for a dataset of 309 Nitrogen heterocycles screened for NMT inhibitory activity. Hundreds of QSAR models were derived. Of these, the model 1 and 2 were chosen as they not only fulfil the recommended values for a good number of validation parameters (e.g., R2 = 0.77–0.79, Q2LMO = 0.75–0.76, CCCex = 0.86–0.87, Q2-F3 = 0.74–0.76, etc.) but also provide useful insights into the structural features that sway the Hs-NMT inhibitory activity of Nitrogen heterocycles. That is, they have an acceptable equipoise of descriptive and predictive qualities as per Organisation for Economic Co-operation and Development (OECD) guidelines. The developed QSAR models identified a good number of molecular descriptors like solvent accessible surface area of all atoms having specific partial charge, absolute surface area of Carbon atoms, etc. as important features to be considered in future optimizations. In addition, pharmacophore modeling has been performed to get additional insight into the pharmacophoric features, which provided additional results.
- Subjects :
- Models, Molecular
Quantitative structure–activity relationship
Pharmaceutical Science
Quantitative Structure-Activity Relationship
Computational biology
01 natural sciences
Article
Analytical Chemistry
Accessible surface area
lcsh:QD241-441
Partial charge
lcsh:Organic chemistry
human N-Myristoyltransferase
statistical analysis
Heterocyclic Compounds
Molecular descriptor
Drug Discovery
N-myristoyltransferase
Humans
Statistical analysis
Physical and Theoretical Chemistry
Enzyme Inhibitors
010405 organic chemistry
Chemistry
QSAR
Organic Chemistry
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Chemistry (miscellaneous)
Drug Design
pharmacophore modeling
Molecular Medicine
nitrogen heterocycles
Pharmacophore
Acyltransferases
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....4ee924320cf1ac0c7c4dc6711a47c49b