Synthesis and in silico screening of a library of β-carboline-containing compounds
The synthesis of a library of tetrahydro-β-carboline-containing compounds in milligram quantities is described. Among the unique heterocyclic frameworks are twelve tetrahydroindolizinoindoles, six tetrahydrocyclobutanindoloquinolizinones and three tetrahydrocyclopentenoneindolizinoindolones. These c...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Beilstein-Institut
2012-07-01
|
| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.8.117 |
| _version_ | 1818912145931239424 |
|---|---|
| author | Kay M. Brummond John R. Goodell Matthew G. LaPorte Lirong Wang Xiang-Qun Xie |
| author_facet | Kay M. Brummond John R. Goodell Matthew G. LaPorte Lirong Wang Xiang-Qun Xie |
| author_sort | Kay M. Brummond |
| collection | DOAJ |
| description | The synthesis of a library of tetrahydro-β-carboline-containing compounds in milligram quantities is described. Among the unique heterocyclic frameworks are twelve tetrahydroindolizinoindoles, six tetrahydrocyclobutanindoloquinolizinones and three tetrahydrocyclopentenoneindolizinoindolones. These compounds were selected from a virtual combinatorial library of 11,478 compounds. Physical chemical properties were calculated and most of them are in accordance with Lipinski’s rules. Virtual docking and ligand-based target evaluations were performed for the β-carboline library compounds and selected synthetic intermediates to assess the therapeutic potential of these small organic molecules. These compounds have been deposited into the NIH Molecular Repository (MLSMR) and may target proteins such as histone deacetylase 4, endothelial nitric oxide synthase, 5-hydroxytryptamine receptor 6 and mitogen-activated protein kinase 1. These in silico screening results aim to add value to the β-carboline library of compounds for those interested in probes of these targets. |
| first_indexed | 2024-12-19T23:09:57Z |
| format | Article |
| id | doaj.art-e2e91948709e45f8a42168178499e068 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-19T23:09:57Z |
| publishDate | 2012-07-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-e2e91948709e45f8a42168178499e0682022-12-21T20:02:16ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972012-07-01811048105810.3762/bjoc.8.1171860-5397-8-117Synthesis and in silico screening of a library of β-carboline-containing compoundsKay M. Brummond0John R. Goodell1Matthew G. LaPorte2Lirong Wang3Xiang-Qun Xie4Department of Chemistry, Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USADepartment of Chemistry, Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USADepartment of Chemistry, Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USADepartment of Pharmaceutical Sciences and Computational Chemical Genomics Center, School of Pharmacy; Drug Discovery Institute; Department of Computational Biology; University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USADepartment of Pharmaceutical Sciences and Computational Chemical Genomics Center, School of Pharmacy; Drug Discovery Institute; Department of Computational Biology; University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USAThe synthesis of a library of tetrahydro-β-carboline-containing compounds in milligram quantities is described. Among the unique heterocyclic frameworks are twelve tetrahydroindolizinoindoles, six tetrahydrocyclobutanindoloquinolizinones and three tetrahydrocyclopentenoneindolizinoindolones. These compounds were selected from a virtual combinatorial library of 11,478 compounds. Physical chemical properties were calculated and most of them are in accordance with Lipinski’s rules. Virtual docking and ligand-based target evaluations were performed for the β-carboline library compounds and selected synthetic intermediates to assess the therapeutic potential of these small organic molecules. These compounds have been deposited into the NIH Molecular Repository (MLSMR) and may target proteins such as histone deacetylase 4, endothelial nitric oxide synthase, 5-hydroxytryptamine receptor 6 and mitogen-activated protein kinase 1. These in silico screening results aim to add value to the β-carboline library of compounds for those interested in probes of these targets.https://doi.org/10.3762/bjoc.8.117β-carbolinebiological activitychemical diversitydiversity-oriented synthesisin silico screening |
| spellingShingle | Kay M. Brummond John R. Goodell Matthew G. LaPorte Lirong Wang Xiang-Qun Xie Synthesis and in silico screening of a library of β-carboline-containing compounds Beilstein Journal of Organic Chemistry β-carboline biological activity chemical diversity diversity-oriented synthesis in silico screening |
| title | Synthesis and in silico screening of a library of β-carboline-containing compounds |
| title_full | Synthesis and in silico screening of a library of β-carboline-containing compounds |
| title_fullStr | Synthesis and in silico screening of a library of β-carboline-containing compounds |
| title_full_unstemmed | Synthesis and in silico screening of a library of β-carboline-containing compounds |
| title_short | Synthesis and in silico screening of a library of β-carboline-containing compounds |
| title_sort | synthesis and in silico screening of a library of β carboline containing compounds |
| topic | β-carboline biological activity chemical diversity diversity-oriented synthesis in silico screening |
| url | https://doi.org/10.3762/bjoc.8.117 |
| work_keys_str_mv | AT kaymbrummond synthesisandinsilicoscreeningofalibraryofbcarbolinecontainingcompounds AT johnrgoodell synthesisandinsilicoscreeningofalibraryofbcarbolinecontainingcompounds AT matthewglaporte synthesisandinsilicoscreeningofalibraryofbcarbolinecontainingcompounds AT lirongwang synthesisandinsilicoscreeningofalibraryofbcarbolinecontainingcompounds AT xiangqunxie synthesisandinsilicoscreeningofalibraryofbcarbolinecontainingcompounds |