Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors
Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in many biological processes and is considered as a potential target for anticancer therapy. Although some PARP-1 inhibitors have been reported, their clinical application in cancer therapy is limited by some shortcomings such as weak affi...
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| Format: | Article |
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MDPI AG
2019-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/23/4258 |
| _version_ | 1818363657971564544 |
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| author | Yunjiang Zhou Shi Tang Tingting Chen Miao-Miao Niu |
| author_facet | Yunjiang Zhou Shi Tang Tingting Chen Miao-Miao Niu |
| author_sort | Yunjiang Zhou |
| collection | DOAJ |
| description | Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in many biological processes and is considered as a potential target for anticancer therapy. Although some PARP-1 inhibitors have been reported, their clinical application in cancer therapy is limited by some shortcomings such as weak affinity, low selectivity and adverse side effects. To identify highly potent and selective PARP-1 inhibitors, an integrated protocol that combines pharmacophore mapping, virtual screening and molecular docking was constructed. It was then used as a screening query to identify potent leads with unknown scaffolds from an in-house database. Finally, four retrieved compounds were selected for biological evaluation. Biological testing indicated that the four compounds showed strong inhibitory activities on the PARP-1 (<i>IC<sub>50</sub></i> < 0.2 μM). MTT assay confirmed that compounds <b>1</b>−<b>4</b> inhibited the growth of human lung cancer A549 cells in a dose-dependent manner. The obtained compounds from this study may be potential leads for PARP-1 inhibition in the treatment of cancer. |
| first_indexed | 2024-12-13T21:51:58Z |
| format | Article |
| id | doaj.art-56c06118023a40b7a0c543b9b6bc3cd2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T21:51:58Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-56c06118023a40b7a0c543b9b6bc3cd22022-12-21T23:30:14ZengMDPI AGMolecules1420-30492019-11-012423425810.3390/molecules24234258molecules24234258Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) InhibitorsYunjiang Zhou0Shi Tang1Tingting Chen2Miao-Miao Niu3Department of Pharmaceutical Analysis, State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaDepartment of Pharmaceutical Analysis, State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaDepartment of Pharmaceutical Analysis, State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaDepartment of Pharmaceutical Analysis, State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaPoly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in many biological processes and is considered as a potential target for anticancer therapy. Although some PARP-1 inhibitors have been reported, their clinical application in cancer therapy is limited by some shortcomings such as weak affinity, low selectivity and adverse side effects. To identify highly potent and selective PARP-1 inhibitors, an integrated protocol that combines pharmacophore mapping, virtual screening and molecular docking was constructed. It was then used as a screening query to identify potent leads with unknown scaffolds from an in-house database. Finally, four retrieved compounds were selected for biological evaluation. Biological testing indicated that the four compounds showed strong inhibitory activities on the PARP-1 (<i>IC<sub>50</sub></i> < 0.2 μM). MTT assay confirmed that compounds <b>1</b>−<b>4</b> inhibited the growth of human lung cancer A549 cells in a dose-dependent manner. The obtained compounds from this study may be potential leads for PARP-1 inhibition in the treatment of cancer.https://www.mdpi.com/1420-3049/24/23/4258parp-1virtual screeningpharmacophore modelingmolecular docking |
| spellingShingle | Yunjiang Zhou Shi Tang Tingting Chen Miao-Miao Niu Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Molecules parp-1 virtual screening pharmacophore modeling molecular docking |
| title | Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors |
| title_full | Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors |
| title_fullStr | Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors |
| title_full_unstemmed | Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors |
| title_short | Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors |
| title_sort | structure based pharmacophore modeling virtual screening molecular docking and biological evaluation for identification of potential poly adp ribose polymerase 1 parp 1 inhibitors |
| topic | parp-1 virtual screening pharmacophore modeling molecular docking |
| url | https://www.mdpi.com/1420-3049/24/23/4258 |
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