Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/105271
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Baptista, João A. | - |
dc.contributor.author | Rosado, Mário T. S. | - |
dc.contributor.author | Castro, Ricardo A. E. | - |
dc.contributor.author | Évora, António O. L. | - |
dc.contributor.author | Maria, Teresa M. R. | - |
dc.contributor.author | Silva, Manuela Ramos | - |
dc.contributor.author | Canotilho, João | - |
dc.contributor.author | Eusébio, M. Ermelinda S. | - |
dc.date.accessioned | 2023-02-13T13:05:46Z | - |
dc.date.available | 2023-02-13T13:05:46Z | - |
dc.date.issued | 2021-11-06 | - |
dc.identifier.issn | 1420-3049 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/105271 | - |
dc.description.abstract | In this work, co-crystal screening was carried out for two important dihydrofolate reductase (DHFR) inhibitors, trimethoprim (TMP) and pyrimethamine (PMA), and for 2,4-diaminopyrimidine (DAP), which is the pharmacophore of these active pharmaceutical ingredients (API). The isomeric pyridinecarboxamides and two xanthines, theophylline (THEO) and caffeine (CAF), were used as co-formers in the same experimental conditions, in order to evaluate the potential for the pharmacophore to be used as a guide in the screening process. In silico co-crystal screening was carried out using BIOVIA COSMOquick and experimental screening was performed by mechanochemistry and supported by (solid + liquid) binary phase diagrams, infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD). The in silico prediction of low propensities for DAP, TMP and PMA to co-crystallize with pyridinecarboxamides was confirmed: a successful outcome was only observed for DAP + nicotinamide. Successful synthesis of multicomponent solid forms was achieved for all three target molecules with theophylline, with DAP co-crystals revealing a greater variety of stoichiometries. The crystalline structures of a (1:2) TMP:THEO co-crystal and of a (1:2:1) DAP:THEO:ethyl acetate solvate were solved. This work demonstrated the possible use of the pharmacophore of DHFR inhibitors as a guide for co-crystal screening, recognizing some similar trends in the outcome of association in the solid state and in the molecular aggregation in the co-crystals, characterized by the same supramolecular synthons. | pt |
dc.language.iso | eng | pt |
dc.publisher | MDPI | pt |
dc.relation | UID/QUI/00313/2020 | pt |
dc.relation | UI/BD/150859/2021 | pt |
dc.relation | SFRH/BPD/115697/2016 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | co-crystal screening | pt |
dc.subject | dihydrofolate reductase inhibitors | pt |
dc.subject | pharmacophore | pt |
dc.subject | trimethoprim | pt |
dc.subject | pyrimethamine | pt |
dc.subject | 2,4-diaminopyrimidine | pt |
dc.subject | pyridinecarboxamides | pt |
dc.subject | theophylline | pt |
dc.subject | caffeine | pt |
dc.subject.mesh | Crystallography, X-Ray | pt |
dc.subject.mesh | Drug Evaluation, Preclinical | pt |
dc.subject.mesh | Enzyme Inhibitors | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Models, Molecular | pt |
dc.subject.mesh | Molecular Structure | pt |
dc.subject.mesh | Pyrimethamine | pt |
dc.subject.mesh | Pyrimidines | pt |
dc.subject.mesh | Tetrahydrofolate Dehydrogenase | pt |
dc.subject.mesh | Trimethoprim | pt |
dc.title | Dihydrofolate Reductase Inhibitors: The Pharmacophore as a Guide for Co-Crystal Screening | pt |
dc.type | article | - |
degois.publication.firstPage | 6721 | pt |
degois.publication.issue | 21 | pt |
degois.publication.title | Molecules | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3390/molecules26216721 | pt |
degois.publication.volume | 26 | pt |
dc.date.embargo | 2021-11-06 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.orcid | 0000-0002-3822-4398 | - |
crisitem.author.orcid | 0000-0001-5782-8819 | - |
crisitem.author.orcid | 0000-0002-1263-9034 | - |
crisitem.author.orcid | 0000-0002-7143-2228 | - |
crisitem.author.orcid | 0000-0001-9555-8856 | - |
crisitem.author.orcid | 0000-0001-6045-2330 | - |
crisitem.author.orcid | 0000-0002-5515-7721 | - |
Appears in Collections: | I&D CQC - Artigos em Revistas Internacionais I&D CFis - Artigos em Revistas Internacionais |
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Dihydrofolate-reductase-inhibitors-The-pharmacophore-as-a-guide-for-cocrystal-screeningMolecules.pdf | 8.33 MB | Adobe PDF | View/Open |
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