Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide
Dihydrofolate reductase (DHFR) plays a vital role in the DNA synthesis by reducing dihydrofolic acid to tetrahydrofolic acid which is an essential component. Synthetic ligands like methotrexate (MTX), aminopterin (AMP) and their analogues act as potential anti metabolites by mimicking the coenzyme d...
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| Format: | Article |
| Language: | English |
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Wiley
2008-01-01
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| Series: | E-Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2008/401738 |
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| author | Lingala Yamini Manga Vijjulatha |
| author_facet | Lingala Yamini Manga Vijjulatha |
| author_sort | Lingala Yamini |
| collection | DOAJ |
| description | Dihydrofolate reductase (DHFR) plays a vital role in the DNA synthesis by reducing dihydrofolic acid to tetrahydrofolic acid which is an essential component. Synthetic ligands like methotrexate (MTX), aminopterin (AMP) and their analogues act as potential anti metabolites by mimicking the coenzyme dihydrofolic acid (DHFA) they inhibit the activity of DHFR antagonistically. Several ligands which are similar to MTX analogues and 6, 8 substituted 2 – naphthyls (NAP) which can mimic the pteridyl group of DHFA have been computationally designed. These ligands were proposed to hinder the formation N5, N10 methylene tetrahydrofolic acid (THFA) coenzyme, which is essential for the DNA synthesis. The docking studies were done using grid, generated with the 0.9 Vander Waals scaling for non polar bonds in the active site of the receptor. These newly designed ligands such as 14 -21 ,23 and 28 have shown good docking scores and predicted activities when compared to already existing ligands MTX and its analogues. |
| format | Article |
| id | doaj-art-b9b28f9990ec40c7b4d8f9d957a321a8 |
| institution | Kabale University |
| issn | 0973-4945 2090-9810 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | E-Journal of Chemistry |
| spelling | doaj-art-b9b28f9990ec40c7b4d8f9d957a321a82025-02-03T06:00:32ZengWileyE-Journal of Chemistry0973-49452090-98102008-01-015226327010.1155/2008/401738Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using GlideLingala Yamini0Manga Vijjulatha1Department of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad, 500 001, IndiaDepartment of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad, 500 001, IndiaDihydrofolate reductase (DHFR) plays a vital role in the DNA synthesis by reducing dihydrofolic acid to tetrahydrofolic acid which is an essential component. Synthetic ligands like methotrexate (MTX), aminopterin (AMP) and their analogues act as potential anti metabolites by mimicking the coenzyme dihydrofolic acid (DHFA) they inhibit the activity of DHFR antagonistically. Several ligands which are similar to MTX analogues and 6, 8 substituted 2 – naphthyls (NAP) which can mimic the pteridyl group of DHFA have been computationally designed. These ligands were proposed to hinder the formation N5, N10 methylene tetrahydrofolic acid (THFA) coenzyme, which is essential for the DNA synthesis. The docking studies were done using grid, generated with the 0.9 Vander Waals scaling for non polar bonds in the active site of the receptor. These newly designed ligands such as 14 -21 ,23 and 28 have shown good docking scores and predicted activities when compared to already existing ligands MTX and its analogues.http://dx.doi.org/10.1155/2008/401738 |
| spellingShingle | Lingala Yamini Manga Vijjulatha Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide E-Journal of Chemistry |
| title | Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide |
| title_full | Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide |
| title_fullStr | Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide |
| title_full_unstemmed | Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide |
| title_short | Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide |
| title_sort | inhibitors of human dihydrofolate reductase a computational design and docking studies using glide |
| url | http://dx.doi.org/10.1155/2008/401738 |
| work_keys_str_mv | AT lingalayamini inhibitorsofhumandihydrofolatereductaseacomputationaldesignanddockingstudiesusingglide AT mangavijjulatha inhibitorsofhumandihydrofolatereductaseacomputationaldesignanddockingstudiesusingglide |