Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents
Isoquinoline derivatives exhibit a range of biological properties, including antibacterial activity, and are thus attractive as a scaffold for developing broad-spectrum antibacterial compounds. A series of six isoquinoline-based compounds were synthesized using the reaction of 6,7-dimethoxy-1-methyl...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | BioChem |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-6411/5/1/1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850204059767668736 |
|---|---|
| author | Matthew J. A. Phillips Alison T. Ung Elizabeth J. Harry Jason Ashmore Andrew M. McDonagh |
| author_facet | Matthew J. A. Phillips Alison T. Ung Elizabeth J. Harry Jason Ashmore Andrew M. McDonagh |
| author_sort | Matthew J. A. Phillips |
| collection | DOAJ |
| description | Isoquinoline derivatives exhibit a range of biological properties, including antibacterial activity, and are thus attractive as a scaffold for developing broad-spectrum antibacterial compounds. A series of six isoquinoline-based compounds were synthesized using the reaction of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline with dimethyl acetylenedicarboxylate (DMAD) to provide the tricyclic (2Z)-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate. The [2 + 3] cycloaddition of DMAD with C-6 and C-7 substituted 1-methyl-3,4-dihydroisoquinolines proceeded using aryl ethers or unsubstituted compounds, but not with amine, amide or nitro moieties at the C-7 position. Compounds <b>8d</b> and <b>8f</b> were found to have antibacterial properties against some Gram-positive pathogens (<i>Staphylococcus aureus</i>—<b>8d</b> = 16 µg/mL, <b>8f</b> = 32 µg/mL; <i>Streptococcus pneumoniae—</i><b>8f</b> = 32 µg/mL; and <i>Enterococcus faecium—</i><b>8d</b> = 128 µg/mL, <b>8f</b> = 64 µg/mL). Evaluation of their cytotoxic properties against mammalian cell lines revealed some cytotoxic effects (<b>8b</b> and <b>8d</b>, 125 µM, 24 h, HEp-2 cells) and (<b>8a</b>, <b>8b</b>, <b>8d</b> = 125 µM, <b>8f</b> = 62.5 µM, 24 h, McCoy B cells), suggesting limitations in their antibacterial applications without further development. |
| format | Article |
| id | doaj-art-3791ba7b065e42b8885151cbfb53bbf3 |
| institution | OA Journals |
| issn | 2673-6411 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | BioChem |
| spelling | doaj-art-3791ba7b065e42b8885151cbfb53bbf32025-08-20T02:11:22ZengMDPI AGBioChem2673-64112024-12-0151110.3390/biochem5010001Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial AgentsMatthew J. A. Phillips0Alison T. Ung1Elizabeth J. Harry2Jason Ashmore3Andrew M. McDonagh4School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaSchool of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaAustralian Institute for Microbiology & Infection, University of Technology Sydney, Sydney, NSW 2007, AustraliaSchool of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaSchool of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaIsoquinoline derivatives exhibit a range of biological properties, including antibacterial activity, and are thus attractive as a scaffold for developing broad-spectrum antibacterial compounds. A series of six isoquinoline-based compounds were synthesized using the reaction of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline with dimethyl acetylenedicarboxylate (DMAD) to provide the tricyclic (2Z)-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate. The [2 + 3] cycloaddition of DMAD with C-6 and C-7 substituted 1-methyl-3,4-dihydroisoquinolines proceeded using aryl ethers or unsubstituted compounds, but not with amine, amide or nitro moieties at the C-7 position. Compounds <b>8d</b> and <b>8f</b> were found to have antibacterial properties against some Gram-positive pathogens (<i>Staphylococcus aureus</i>—<b>8d</b> = 16 µg/mL, <b>8f</b> = 32 µg/mL; <i>Streptococcus pneumoniae—</i><b>8f</b> = 32 µg/mL; and <i>Enterococcus faecium—</i><b>8d</b> = 128 µg/mL, <b>8f</b> = 64 µg/mL). Evaluation of their cytotoxic properties against mammalian cell lines revealed some cytotoxic effects (<b>8b</b> and <b>8d</b>, 125 µM, 24 h, HEp-2 cells) and (<b>8a</b>, <b>8b</b>, <b>8d</b> = 125 µM, <b>8f</b> = 62.5 µM, 24 h, McCoy B cells), suggesting limitations in their antibacterial applications without further development.https://www.mdpi.com/2673-6411/5/1/1antibacterialisoquinoline3,4-dihydroisoquinolinecytotoxicity |
| spellingShingle | Matthew J. A. Phillips Alison T. Ung Elizabeth J. Harry Jason Ashmore Andrew M. McDonagh Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents BioChem antibacterial isoquinoline 3,4-dihydroisoquinoline cytotoxicity |
| title | Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents |
| title_full | Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents |
| title_fullStr | Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents |
| title_full_unstemmed | Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents |
| title_short | Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents |
| title_sort | synthesis and investigation of tricyclic isoquinoline derivatives as antibacterial agents |
| topic | antibacterial isoquinoline 3,4-dihydroisoquinoline cytotoxicity |
| url | https://www.mdpi.com/2673-6411/5/1/1 |
| work_keys_str_mv | AT matthewjaphillips synthesisandinvestigationoftricyclicisoquinolinederivativesasantibacterialagents AT alisontung synthesisandinvestigationoftricyclicisoquinolinederivativesasantibacterialagents AT elizabethjharry synthesisandinvestigationoftricyclicisoquinolinederivativesasantibacterialagents AT jasonashmore synthesisandinvestigationoftricyclicisoquinolinederivativesasantibacterialagents AT andrewmmcdonagh synthesisandinvestigationoftricyclicisoquinolinederivativesasantibacterialagents |