Computer-aided design, synthesis, and characterization of molecular hybrids of dihydropyrazoles, aminopyrimidines, and thiazolidin-4-ones as potential inhibitors of the penicillin-binding protein 3 (PBP-3) of Escherichia coli
A computer-assisted approach was used to model and study privileged heterocyclic scaffolds containing dihydropyrazole, pyrimidin-2-amine, and thiazolidin-4-one moieties (hybrid pharmacophores) to obtain novel and promising antimicrobial prototype molecules. Main bioavailability descriptors were d...
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| Format: | article |
| Langue: | EN ES |
| Publié: |
Pontificia Universidad Javeriana
2021
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| Accès en ligne: | https://doaj.org/article/7bae2324ad9548a98c2a4823fc69d2b4 |
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| Résumé: | A computer-assisted approach was used to model and study privileged heterocyclic scaffolds containing
dihydropyrazole, pyrimidin-2-amine, and thiazolidin-4-one moieties (hybrid pharmacophores) to
obtain novel and promising antimicrobial prototype molecules. Main bioavailability descriptors
were determined in order to assess the drug-likeness of the designed compounds and to pre-filter
eleven compounds exhibiting the best profiles, thus passing to molecular docking study against a key
penicillin-binding protein type-3 from enterotoxygenic E. coli. Seven structures were chosen by their
energies of affinity and docking interactions with key residues in the active site of the receptor. Seven
compounds with the highest docking scores belonging to the series of chalcones, dihydropyrazoles,
aminopyrimidines, and thiazolidin-4-ones were prepared via condensation or cyclocondensation
reactions. The structural elucidation of the final products was carried out by infrared spectra analysis
and NMR experiments. Such molecular hybrids considered as potential hits in the search for new
antibacterial compounds will be tested in vitro in further studies. |
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