Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides
Despite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/8/768 |
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| author | Ghada Bouz Sarah Bouz Ondřej Janďourek Klára Konečná Pavel Bárta Jarmila Vinšová Martin Doležal Jan Zitko |
| author_facet | Ghada Bouz Sarah Bouz Ondřej Janďourek Klára Konečná Pavel Bárta Jarmila Vinšová Martin Doležal Jan Zitko |
| author_sort | Ghada Bouz |
| collection | DOAJ |
| description | Despite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a series of their ortho fused derivatives, <i>N</i>-phenyl- and <i>N</i>-benzyl quinoxaline-2-carboxamides, and evaluated their in vitro antimycobacterial activity. In vitro activity against <i>Mycobacterium tuberculosis</i> H37Ra (represented by minimum inhibitory concentration, MIC) ranged between 3.91–500 µg/mL, with most compounds having moderate to good activities (MIC < 15.625 µg/mL). The majority of the active compounds belonged to the <i>N</i>-benzyl group. In addition to antimycobacterial activity assessment, final compounds were screened for their in vitro cytotoxicity. <i>N</i>-(naphthalen-1-ylmethyl)quinoxaline-2-carboxamide (compound <b>29</b>) was identified as a potential antineoplastic agent with selective cytotoxicity against hepatic (HepG2), ovarian (SK-OV-3), and prostate (PC-3) cancer cells lines. Molecular docking showed that human DNA topoisomerase and vascular endothelial growth factor receptor could be potential targets for <b>29</b>. |
| first_indexed | 2024-03-10T08:29:26Z |
| format | Article |
| id | doaj.art-9837cdb516af40088446b84f4bb1efd2 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T08:29:26Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-9837cdb516af40088446b84f4bb1efd22023-11-22T09:11:31ZengMDPI AGPharmaceuticals1424-82472021-08-0114876810.3390/ph14080768Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-CarboxamidesGhada Bouz0Sarah Bouz1Ondřej Janďourek2Klára Konečná3Pavel Bárta4Jarmila Vinšová5Martin Doležal6Jan Zitko7Faculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicFaculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech RepublicDespite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a series of their ortho fused derivatives, <i>N</i>-phenyl- and <i>N</i>-benzyl quinoxaline-2-carboxamides, and evaluated their in vitro antimycobacterial activity. In vitro activity against <i>Mycobacterium tuberculosis</i> H37Ra (represented by minimum inhibitory concentration, MIC) ranged between 3.91–500 µg/mL, with most compounds having moderate to good activities (MIC < 15.625 µg/mL). The majority of the active compounds belonged to the <i>N</i>-benzyl group. In addition to antimycobacterial activity assessment, final compounds were screened for their in vitro cytotoxicity. <i>N</i>-(naphthalen-1-ylmethyl)quinoxaline-2-carboxamide (compound <b>29</b>) was identified as a potential antineoplastic agent with selective cytotoxicity against hepatic (HepG2), ovarian (SK-OV-3), and prostate (PC-3) cancer cells lines. Molecular docking showed that human DNA topoisomerase and vascular endothelial growth factor receptor could be potential targets for <b>29</b>.https://www.mdpi.com/1424-8247/14/8/768antimycobacterialcytotoxicitymolecular docking<i>Mycobacterium tuberculosis</i>pyrazinamidequinoxaline |
| spellingShingle | Ghada Bouz Sarah Bouz Ondřej Janďourek Klára Konečná Pavel Bárta Jarmila Vinšová Martin Doležal Jan Zitko Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides Pharmaceuticals antimycobacterial cytotoxicity molecular docking <i>Mycobacterium tuberculosis</i> pyrazinamide quinoxaline |
| title | Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides |
| title_full | Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides |
| title_fullStr | Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides |
| title_full_unstemmed | Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides |
| title_short | Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides |
| title_sort | synthesis biological evaluation and in silico modeling of i n i substituted quinoxaline 2 carboxamides |
| topic | antimycobacterial cytotoxicity molecular docking <i>Mycobacterium tuberculosis</i> pyrazinamide quinoxaline |
| url | https://www.mdpi.com/1424-8247/14/8/768 |
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