Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors
In this report, we describe the structural characterization of three 2,4-disubstituted-dihydropyrimidine-5-carbonitrile derivatives, namely 2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-4-propyl-1,6-dihydropyrimidine-5-carbonitrile <b>1</b>, 4-(2-methylpropyl)-2-{[(4-nitrophenyl)methyl]sulfa...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/11/3286 |
| _version_ | 1797532035159425024 |
|---|---|
| author | Lamya H. Al-Wahaibi Althaf Shaik Mohammed A. Elmorsy Mohammed S. M. Abdelbaky Santiago Garcia-Granda Subbiah Thamotharan Vijay Thiruvenkatam Ali A. El-Emam |
| author_facet | Lamya H. Al-Wahaibi Althaf Shaik Mohammed A. Elmorsy Mohammed S. M. Abdelbaky Santiago Garcia-Granda Subbiah Thamotharan Vijay Thiruvenkatam Ali A. El-Emam |
| author_sort | Lamya H. Al-Wahaibi |
| collection | DOAJ |
| description | In this report, we describe the structural characterization of three 2,4-disubstituted-dihydropyrimidine-5-carbonitrile derivatives, namely 2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-4-propyl-1,6-dihydropyrimidine-5-carbonitrile <b>1</b>, 4-(2-methylpropyl)-2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-1,6-dihydropyrimidine-5-carbonitrile <b>2</b>, and 2-[(2-ethoxyethyl)sulfanyl]-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile monohydrate <b>3</b>. An X-ray diffraction analysis revealed that these compounds were crystallized in the centrosymmetric space groups and adopt an L-shaped conformation. One of the compounds (<b>3</b>) crystallized with a water molecule. A cyclic motif (R<sub>2</sub><sup>2</sup>(8)) mediated by N–H···O hydrogen bond was formed in compounds <b>1</b> and <b>2</b>, whereas the corresponding motif was not favorable, due to the water molecule, in compound <b>3</b>. The crystal packing of these compounds was analyzed based on energy frameworks performed at the B3LYP/6-31G(d,p) level of theory. Various inter-contacts were characterized using the Hirshfeld surface and its associated 2D-fingerprint plots. Furthermore, a molecular docking simulation was carried out to assess the inhibitory potential of the title compounds against the human dihydrofolate reductase (DHFR) enzyme. |
| first_indexed | 2024-03-10T10:53:19Z |
| format | Article |
| id | doaj.art-136ba6c9f237495b809dc925903b728b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:53:19Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-136ba6c9f237495b809dc925903b728b2023-11-21T22:00:33ZengMDPI AGMolecules1420-30492021-05-012611328610.3390/molecules26113286Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase InhibitorsLamya H. Al-Wahaibi0Althaf Shaik1Mohammed A. Elmorsy2Mohammed S. M. Abdelbaky3Santiago Garcia-Granda4Subbiah Thamotharan5Vijay Thiruvenkatam6Ali A. El-Emam7Department of Chemistry, College of Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi ArabiaDiscipline of Chemistry, Indian Institute of Technology, Gandhinagar 382355, IndiaDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Physical and Analytical Chemistry, Faculty of Chemistry, Oviedo University-CINN, 33006 Oviedo, SpainDepartment of Physical and Analytical Chemistry, Faculty of Chemistry, Oviedo University-CINN, 33006 Oviedo, SpainBiomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, IndiaDiscipline of Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat 382355, IndiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptIn this report, we describe the structural characterization of three 2,4-disubstituted-dihydropyrimidine-5-carbonitrile derivatives, namely 2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-4-propyl-1,6-dihydropyrimidine-5-carbonitrile <b>1</b>, 4-(2-methylpropyl)-2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-1,6-dihydropyrimidine-5-carbonitrile <b>2</b>, and 2-[(2-ethoxyethyl)sulfanyl]-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile monohydrate <b>3</b>. An X-ray diffraction analysis revealed that these compounds were crystallized in the centrosymmetric space groups and adopt an L-shaped conformation. One of the compounds (<b>3</b>) crystallized with a water molecule. A cyclic motif (R<sub>2</sub><sup>2</sup>(8)) mediated by N–H···O hydrogen bond was formed in compounds <b>1</b> and <b>2</b>, whereas the corresponding motif was not favorable, due to the water molecule, in compound <b>3</b>. The crystal packing of these compounds was analyzed based on energy frameworks performed at the B3LYP/6-31G(d,p) level of theory. Various inter-contacts were characterized using the Hirshfeld surface and its associated 2D-fingerprint plots. Furthermore, a molecular docking simulation was carried out to assess the inhibitory potential of the title compounds against the human dihydrofolate reductase (DHFR) enzyme.https://www.mdpi.com/1420-3049/26/11/3286pyrimidine-5-carbonitrilesdihydrofolate reductasecrystal structureDFTHirshfeld surface analysis |
| spellingShingle | Lamya H. Al-Wahaibi Althaf Shaik Mohammed A. Elmorsy Mohammed S. M. Abdelbaky Santiago Garcia-Granda Subbiah Thamotharan Vijay Thiruvenkatam Ali A. El-Emam Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors Molecules pyrimidine-5-carbonitriles dihydrofolate reductase crystal structure DFT Hirshfeld surface analysis |
| title | Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors |
| title_full | Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors |
| title_fullStr | Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors |
| title_full_unstemmed | Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors |
| title_short | Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors |
| title_sort | structural insights of three 2 4 disubstituted dihydropyrimidine 5 carbonitriles as potential dihydrofolate reductase inhibitors |
| topic | pyrimidine-5-carbonitriles dihydrofolate reductase crystal structure DFT Hirshfeld surface analysis |
| url | https://www.mdpi.com/1420-3049/26/11/3286 |
| work_keys_str_mv | AT lamyahalwahaibi structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT althafshaik structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT mohammedaelmorsy structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT mohammedsmabdelbaky structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT santiagogarciagranda structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT subbiahthamotharan structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT vijaythiruvenkatam structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors AT aliaelemam structuralinsightsofthree24disubstituteddihydropyrimidine5carbonitrilesaspotentialdihydrofolatereductaseinhibitors |