Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemistry
2.1.1. Synthesis of 3-Methoxybenzaldehyde (2)
2.1.2. General Procedure for the Synthesis of Nitrostyrene Compounds (3a–3c)
- 3-Methoxy-β-nitrostyrene (3a) (6.80 g, 93%) from 3-hydroxybenzaldehyde over two steps. 1H NMR: (500 MHz, CDCl3) δ 7.97 (d, J = 14.0 Hz, 1H, H-2′), 7.57 (d, J = 13.5 Hz, 1H, H-1′), 7.36 (dd, J = 9.0, 7.5 Hz, 1H, H-5), 7.05–7.03 (m, 2H, 2H-Ar), 3.85 (s, 3H, OCH3). 13C NMR: (125 MHz, CDCl3) δ 160.1, 139.0, 137.3, 131.3, 130.4, 121.7, 117.9, 114.0, 55.4. Spectral data were consistent with reported values [19].
- 4-Methoxy-β-nitrostyrene (3b) (5.21 g, 79%). 1H NMR: (500 MHz, CDCl3) δ 7.90 (d, J = 13.5 Hz, 1H, H-2′), 7.51 (d, J = 13.5 Hz, 1H, H-1′), 7.49 (d, J = 9.0 Hz, 2H, H-2, 6), 6.95 (d, J = 9.0 Hz, 2H, H-3, 5), 3.86 (s, 3H, OCH3). 13C NMR: (125 MHz, CDCl3) δ 162.9, 139.0, 135.0 131.1, 122.5, 114.9, 55.5. Spectral data were consistent with reported values [20].
- 3,4-Dimethoxy-β-nitrostyrene (3c) (2.75 g, 71%) 1H NMR: (500 MHz, CDCl3) δ 7.93 (d, J = 13.5 Hz, 1H, H-2′), 7.47 (d, J = 13.0 Hz, 1H, H-1′), 7.07 (dd, J = 8.0, 1.5 Hz, 1H, H-6), 7.00 (d, J = 1.0 Hz, 1H, H-2), 6.87 (d, J = 8.0 Hz, 1H, H-5), 6.06 (s, 2H, CH2). 13C NMR: (125 MHz, CDCl3) δ 151.4, 148.8, 139.1, 135.4, 126.6, 124.2, 109.1, 107.0, 102.0. Spectral data were consistent with reported values [21].
2.1.3. General Procedure for the Synthesis of Phenylethylamines (4a–c)
- 2-(3-Methoxyphenyl)ethylamine (4a) Yellow oil (2.00 g, 35%). 1H NMR: (500 MHz, CDCl3): δ 7.22 (t, J = 7.5 Hz, 1H H-3), 6.79 (d J = 7.5 Hz, H-2), 6.77–6.76 (m, 1H, H-4), 6.75 (s, 1H, H-6), 3.80 (s, 3H, OCH3), 2.97 (t, J = 7.0 Hz, 2H, H-1″), 2.73 (t, J = 7.0 Hz, 2H, H-1′). 13C NMR: (125 MHz, CDCl3) δ 159.7, 141.4, 129.4, 121.2, 114.6, 111.4, 55.1, 43.4, 40.0. Spectral data were consistent with reported values [23].
- 2-(4-Methoxyphenyl)ethylamine (4b) Yellow oil (2.13 g, 63%). 1H NMR (500 MHz, CDCl3) δ 7.11 (d, J = 9.0 Hz, 2H, H-2, 6), 6.84 (d, J = 8.5 Hz, 2H, H-3, 5), 3.78 (s, 3H, OCH3), 2.92 (t, J = 7.0 Hz, 2H, H-2′), 2.68 (t, J = 7.0 Hz, 2H, H-1′). 13C NMR (125 MHz, CDCl3) δ 158.0, 131.8, 129.7, 133.8, 55.2, 43.7, 39.1. Spectral data were consistent with reported values [24].
- 2-(3,4-Methylenedioxyphenyl)ethylamine (4c) Pale yellow oil (0.731 g, 71%). 1H NMR (500 MHz, CDCl3) δ 6.73 (d, J = 8.0 Hz, 1H, H-5), 6.68 (d, J = 2.0 Hz, 1H, H-2), 6.63 (dd, J = 8.0, 1.5 Hz, 1H, H-6), 5.91 (s, 2H, OCH2O), 2.90 (t, J = 7.0 Hz, 2H, H-2′), 2.65 (t, J = 7.0 Hz, 2H, H-1′) (NH2 Not observed). 13C NMR (125 MHz, CDCl3) δ 147.6, 145.8, 133.5 121.6, 109.1, 108.1, 100.7, 43.6, 39.7. Spectral data were consistent with reported values [21].
2.1.4. General Procedure for the Synthesis of N-Phenylethylacetamides (5a–e)
- N-[2-(3-Methoxyphenyl)ethyl]acetamide (5a) The dark oil was purified by gradient silica gel column chromatography (50–100% ethyl acetate in hexane) to afford a yellow oil (1.86 g, 74%). 1H NMR: (500 MHz, CDCl3) δ 7.23 (t, J = 7.5 Hz, 1H, H-3), 6.77 (d, J = 8.0 Hz, 2H, H-2,4) 6.74 (s, 1H, H-6), 5.50 (br s, 1H, NH), 3.80 (s, 3H, OCH3), 3.51 (q, J = 6.5 Hz, 2H, H-1″), 2.79 (t, J = 7.0 Hz, 2H, H-1′), 1.94 (s, 3H, NHCOCH3). 13C NMR: (125 MHz, CDCl3) δ 170.0, 159.8, 140.4, 129.6, 121.0, 114.4, 111.8, 55.2, 40.5, 35.6, 23.3. Spectral data were consistent with reported values [23].
- N-[2-(4-Methoxyphenyl)ethyl]acetamide (5b) The dark oil was purified by gradient silica gel column chromatography (40–100% ethyl acetate in hexane) to afford a light yellow solid (2.08 g, 77%). 1H NMR: (500 MHz, CDCl3) δ 7.11 (dt, J = 6.5, 1.5 Hz, 2H, H-2, 6), 6.85 (dt, J = 7.0 Hz, 1.5 Hz, 2H, H-3, 5), 5.52 (br s, 1H, NH), 3.79 (s, 3H, OCH3), 3.46 (q, J = 7.0 Hz, 2H, H-2′), 2.75 (t, J = 7.0 Hz, 2H, H-1′), 1.93 (s, 3H, NHCOCH3). 13C NMR: (125 MHz, CDCl3) δ 170.0, 158.2, 130.8, 129.6, 114.0, 55.2, 40.8, 34.7, 23.3. Spectral data were consistent with reported values [25].
- N-[2-(3,4-Methylenedioxyphenyl)ethyl]acetamide (5c) Pale yellow solid (0.543 g, 96%) was used, requiring no further purification. 1H NMR (500 MHz, CDCl3) δ 6.74 (d, J = 8.0 Hz, 1H, H-5), 6.67 (d, J = 2.0 Hz, 1H, H-2), 6.62 (dd, J = 8.0, 2.0 Hz, 1H, H-6), 5.93 (s, 2H, OCH2O), 5.50 (br s. 1H, NH), 3.45 (q, J = 7.0 Hz, 2H, H-2′), 2.72 (t, J = 7.0 Hz, 2H, H-1′), 1.95 (s, 3H, CH3). 13C NMR (125 MHz, CDCl3) δ 170.0, 147.8, 146.2, 132.6, 121.6, 109.0, 108.4, 100.9, 40.8, 35.3, 23.3 Spectral data were consistent with reported values [26].
- N-(2-Phenyl)ethylacetamide (5d) Brown solid requiring no further purification (2.84 g, >99%). 1H NMR: (500 MHz, CDCl3) δ 7.28 (t, J = 7.5 Hz, 2H, 2Ar), 7.20 (d, J = 7.5 Hz, 1H, H-4), 7.17 (t, J = 7.5 Hz, 2H, 2Ar), 6.09 (br s, 1H, NH), 3.46 (q, J = 7.5 Hz, 2H, H-2′), 2.79 (t, J = 7.5 Hz, 2H, H-1′), 1.90 (s, 3H, CH3). 13C NMR: (125 MHz, CDCl3) δ 170.0, 138.8, 128.7, 128.6, 126.5, 40.6, 35.6, 23.3. Spectral data were consistent with reported values [27].
- N-[2-(3,4-Dimethyoxyphenyl)ethyl]acetamide (5e) Yellow solid (3.70 g, >99%). 1H NMR: (500 MHz, CDCl3) δ 6.80–6.79 (m, 1H, H-Ar), 6.72 (m, 2H, 2Ar), 5.56 (br s, 1H, NH), 3.86 (s, 6H, 2 × OCH3), 3.48 (q, J = 7.0 Hz, 2H, H-1′), 2.75 (t, J = 7.0 Hz, 2H, H-2′), 1.93 (s, 3H, COCH3). 13C NMR: (125 MHz, CDCl3) δ 170.0, 149.0, 147.7, 131.3, 129.6, 111.8, 111.4, 111.3, 55.9, 55.8, 40.7, 35.1, 23.3. Spectral data were consistent with reported values [28].
2.1.5. General Procedure for the Synthesis of 1-Methyl-3,4-dihydroisoquinolines (6a–e)
- 6-Methoxy-1-methyl-3,4-dihydroisoquinoline (7a) Yellow oil (1.06 g, 65%). 1H NMR: (500 MHz, CDCl3) δ 7.41 (d, J = 8.5 Hz, 1H, H-8), 6.78 (dd, J = 8.5, 2.0 Hz, 1H, H-7), 6.70 (br s, 1H, H-5), 3.83 (s, 3H, OCH3), 3.62, (t, J = 7.5 Hz, 2H, H-3), 2.68 (t, J = 7.5 Hz, 2H, H-4), 2.34 (br s, 3H, H-1′). 13C NMR: (125 MHz, CDCl3) δ 164.0, 131.1, 139.6, 128.2, 123.1, 112.7, 111.8, 55.3, 46.7, 26.6, 23.2. Spectral data were consistent with reported values [29].
- 7-Methoxy-1-methyl-3,4-dihydroisoquinoline (7b) Yellow oil (0.430 g, 24%). 1H NMR: (500 MHz, CDCl3) 7.09 (d, J = 8.5 Hz, 1H, H-5), 7.02 (d, J = 2.5 Hz, 1H, H-8), 6.90 (dd, J = 8.5, 2.5 Hz, 1H, H-7), 3.82 (s, 3H, OCH3), 3.64 (tq, J = 7.5, 1.5 Hz, 2H, H-3), 2.63 (t, J = 7.5 Hz, 2H, H-4), 2.37 (t, J = 1.5 Hz, 3H, H-1′). 13C NMR: (125 MHz, CDCl3) δ 164.2, 158.4, 130.2, 129.4, 128.1, 115.6, 111.4, 55.4, 47.2, 25.1, 23.2. Spectral data were consistent with reported values [30].
- 6,7-Methylenedioxy-1-methyl-3,4-dihydroisoquinoline (7c) Brown solid that was used without further purification (0.450 g, 62%). 1H NMR: (500 MHz, CDCl3) δ 6.97 (s, 1H, H-8), 6.66 (s, 1H, H-5), 5.97 (s, 2H, OCH2O), 3.59 (td, J = 7.5, 1.5 Hz, 2H, H-3), 2.60 (t, J = 7.5 Hz, 2H, H-4), 2.32 (t, J = 1.5 Hz, 3H, H-1′). 13C NMR: (125 MHz, CDCl3) δ 163.5, 146.3, 132.8, 123.7, 107.8, 106.0, 101.2, 46.9, 26.3, 23.6. Spectral data were consistent with reported values [31].
- Methyl-3,4-dihydroisoquinoline (7d) Brown oil required no further purification. (0.635 g, 74%). 1H NMR: (500 MHz, CDCl3) δ 7.47 (dd, J = 7.5, 1.5 Hz, 1H, H-Ar) 7.34 (td, J = 7.5, 1.5 Hz, 1H, H-Ar), 7.30 (td, J = 7.5, 1.5 Hz, 1H, H-Ar), 7.17, (dd, J = 7.5, 1.5, 1H, H-Ar), 3.66 (tq, J = 7.5, 1.5 Hz, 2H, H-3), 2.70 (t, J = 7.5 Hz, 2H, H-4), 2.38 (s, 3H, CH3). 13C NMR (125 MHz, CDCl3) δ 164.3, 137.4, 130.5, 129.5, 127.4, 126.8, 125.3, 46.9, 26.0, 23.3. Spectral data were consistent with reported values [32].
- 6,7-Dimethoxy-1-methyl-3,4-dihydroisoquinoline (7e) Brown oil was used in the next reaction step without further purification (2.40 g, 72%). 1H NMR: (500 MHz, CDCl3) δ 6.98 (s, 1H, H-8), 6.68 (s, 1H, H-5), 3.90 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 3.62 (td, J = 7.5, 1.5 Hz, 2H, H-3), 2.63 (t, J = 7.5 Hz, 2H, H-4) 2.36 (s, 3H, CH3). 13C NMR: (125 MHz, CDCl3) δ 163.9, 151.0, 147.5, 131.2, 122.3, 110.2, 109.1, 56.2, 56.0, 46.8, 25.7, 23.3. Spectral data were consistent with reported values [33].
2.1.6. Synthesis of (±)-6,7-Dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline (7f)
2.1.7. Synthesis of 7-Nitro-1-methyl-3,4-dihydroisoquinoline (9)
2.1.8. Synthesis of 7-Amino-1-methyl-3,4-dihydroisoquinoline (10)
2.1.9. Synthesis of 7-Acetamido-3,4-dihydro-1-methylisoquinoline Synthesis (11)
2.1.10. Synthesis of Methyl (2Z)-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoates (8a–f)
- Methyl (2Z)-8-methoxy-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate (8a) (20–100% ethyl acetate in hexane) to afford a bright red/orange solid (0.817 g, 52%). 1H NMR: (500 MHz, CDCl3) δ 7.66 (d, J = 8.5 Hz, 1H, H-8), 6.90 (d, J = 9.0 Hz, 1H, H-7), 6.80 (br s, 1H, H-5), 6.05 (s, 1H, C=CH), 5.73 (s, 1H, C=CH), 4.31 (t, J = 6.5 Hz, 2H, H-3), 3.89 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 3.10 (t, J = 6.5 Hz, 2H, H-4). 13C NMR: (125 MHz, CDCl3) δ 187.0, 166.5, 166.3, 163.2, 143.4, 138.9, 130.4, 117.6, 114.1, 113.3, 98.6, 94.3, 55.6, 51.9, 42.2, 29.0. HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C16H16NO4 286.1073; found 286.1110. m.p. 150 °C (decomp.)
- Methyl (2Z)-9-methoxy-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate (8b) (20–40% ethyl acetate in hexane) to afford the desired product as a bright red solid (0.070 g, 11%). 1H NMR: (500 MHz, CDCl3) δ 7.21 (d, J = 8.0 Hz, 1H, H-5), 7.16 (d, J = 2.5 Hz, 1H, H-8), 7.05 (dd, J = 8.0, 2.5 Hz), 6.05 (s, 1H, C=CH), 5.78 (s, 1H, C=CH), 4.27 (t, J = 6.0 Hz, 2H, H-3), 3.85 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 3.04 (t, J = 6.0 Hz, 2H, H-4). 13C NMR: (125 MHz, CDCl3) δ 187.5, 166.3, 166.1, 158.7, 142.8, 129.7, 128.8, 125.7, 119.4, 111.9, 99.3, 95.7, 55.5, 51.9, 42.5, 27.9. HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C16H16NO4 286.1073; found 286.1099. m.p. 151 °C (decomp.)
- Methyl (2Z)-8,9-methylenedioxy-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate (8c) (9:1 dichloromethane/ethyl acetate) affording a bright red solid (0.162 g, 24%). 1H NMR: (500 MHz, CDCl3) δ 7.09 (s, 1H, H-8), 6.75 (s, 1H, H-5), 6.06 (s, 2H, OCH2O), 6.03 (s, 1H, C=CH), 5.67 (s, 1H, C=CH), 4.28 (t, J = 6.5 Hz, 2H, H-3), 3.78 (s, 3H, OCH3), 3.04 (t, J = 6.5 Hz, 3H, H-4). 13C NMR: (125 MHz, CDCl3) δ 187.1, 166.5, 166.0, 151.8, 147.4, 147.4, 143.3, 133.0, 118.5, 108.6, 107.1, 102.0, 98.7, 94.9, 51.9, 42.2, 29.0. HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C16H14NO5 300.0866; found 300.0850. m.p. 199 °C (decomp.)
- Methyl (2Z)-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate (8d) (20–40% ethyl acetate in hexane) to afford a bright red solid (0.080 g, 18%). 1H NMR: (500 MHz, CDCl3) δ 7.71 (d, J = 7.5 Hz, 1H, H-8), 7.48 (t, J = 7.5 Hz, 1H, H-7), 7.37 (t, J = 7.0 Hz, 1H, H-6), 7.31 (d, J = 7.5 Hz, 1H, H-5), 6.06 (s, 1H, C=CH), 5.82 (s, 1H, C=CH), 4.31 (t, J = 6.0 Hz, 2H, H-3), 3.78 (s, 3H, OCH3), 3.12 (t, J = 6.0 Hz, 2H, H-4). 13C NMR: (125 MHz, CDCl3) δ 187.5, 166.4, 166.2, 142.8, 136.4, 132.6, 128.6, 128.1, 127.4, 124.9, 99.3, 95.6, 51.9, 42.3, 28.7. HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd C15H14NO3 256.0968; found 256.1009. m.p. 138 °C (decomp.)
- Methyl (2Z)-8,9-dimethoxy-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate (8e) Triturated with diethyl ether to afford a bright red solid (0.416 g, 83%). 1H NMR: (500 MHz, CDCl3) δ 7.09 (s, 1H, H-8), 6.76 (s, 1H, H-8), 6.03 (s, 1H, C=CH), 5.70 (s, 1H, C=CH), 4.31 (t, J = 6.5 Hz, 2H, H-3), 3.96 (s, 3H, OCH3), 3.92 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 3.06 (t, J = 6.5 Hz, 2H, H-4). 13C NMR: (125 MHz, CDCl3) δ 187.0, 166.5, 166.1, 153.2, 148.5, 143.5, 131.2, 117.1, 110.8, 109.8, 98.5, 94.5, 56.2, 56.2, 51.9, 42.3, 28.4. HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd C17H18NO5 316.1179; found 316.1183. Spectral data were consistent with reported values [16].
- (±)-Methyl (2Z)-8,9-dimethoxy-[2-oxo-5-methyl-5,6-dihydropyrrolo[2,1,a] isoquinolin-3-ylidene]-2-ethanoate (8f) Compound 7f (0.200 g, 1.26 mmol) was dissolved in anhydrous methanol (10 mL) and stirred in a flask at room temperature. DMAD (194 µL, 168 mg, 1.1 equiv.) was added and stirred for 16 h at room temperature. The product precipitated out of the solution as the reaction progressed and was cooled in an ice bath and then filtered. The solid was then washed with cold diethyl ether and dried to give a bright red powder (0.084 g, 28%). 1H NMR: (400 MHz, CDCl3) δ 7.09 (s, 1H, H-6), 6.74 (s, 1H, H-9), 6.05 (s, 1H, H-4″), 5.71 (s, 1H, H-1″), 5.57–5.54 (m, 1H, H-3), 3.96 (s, 3H, -OCH3), 3.93 (s, 3H, -OCH3), 3.78 (s, 3H, -OCH3), 3.42 (dd, J = 6.4, 16.4 Hz, 1H, H-4a), 2.72 (dd, J = 1.6, 16.4 Hz, 1H, H-4b), 1.09 (d, J = 6.8 Hz, 3H, H-3′). 13C NMR: (100 MHz, CDCl3) δ 187.1, 166.4, 164.8, 153.5, 148.3, 142.3, 129.2, 116.6, 111.6, 109.7, 98.6, 94.8, 56.2, 56.1, 51.9, 47.4, 34.4, 18.0 HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd C18H21NO5 330.1336; found 330.1343. m.p. 189 °C (decomp.)
2.2. Biological Studies
2.2.1. MIC Evaluation for Other Bacterial Species (Microdilution Assay)
2.2.2. Cytotoxicity Assay (MTS)
3. Results and Discussion
3.1. Design and Synthesis of Tricyclic Isoquinolines
3.2. Cytotoxicity Evaluation of Synthesized Compounds Against Mammalian Cell Lines
3.3. Evaluation of Antibacterial Properties
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Reaction Time (h) |
---|---|
7a | 4 |
7b | 16 |
7c | 24 |
7d | 3 |
7e | 3 |
Compound | Reaction Time (h) |
---|---|
8a | 1 |
8b | 16 |
8c | 12 |
8d | 16 |
8e | 2 |
8f | 16 |
Compound | R1 | R2 | R3 | MIC (µg/mL) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
S. aureus | E. coli | E. coli ∆tolC | S. pneumoniae | E. faecium | P. aeruginosa | A. baumanii | A. baylyi | ||||
8a | OCH3 | H | H | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 |
8b | H | OCH3 | H | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 |
8c | OCH2O | H | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | |
8d | H | H | H | 16 | >128 | >128 | >32 | 128 | >128 | >32 | >32 |
8e | OCH3 | OCH3 | H | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 |
8f | OCH3 | OCH3 | CH3 | 32 | >128 | >128 | 32 | 64 | >128 | >128 | >128 |
CIP a [11] | - | - | - | 0.25 | ≤0.03 | ≤0.03 | 1 | - | - | - | 0.06 [41] |
MER b [42] | - | - | - | 0.12 | ≤0.06 | - | - | - | 0.5 | 0.5 | - |
VAN c [43] | - | - | - | - | - | - | - | 1 | - | - | - |
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Phillips, M.J.A.; Ung, A.T.; Harry, E.J.; Ashmore, J.; McDonagh, A.M. Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents. BioChem 2025, 5, 1. https://doi.org/10.3390/biochem5010001
Phillips MJA, Ung AT, Harry EJ, Ashmore J, McDonagh AM. Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents. BioChem. 2025; 5(1):1. https://doi.org/10.3390/biochem5010001
Chicago/Turabian StylePhillips, Matthew J. A., Alison T. Ung, Elizabeth J. Harry, Jason Ashmore, and Andrew M. McDonagh. 2025. "Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents" BioChem 5, no. 1: 1. https://doi.org/10.3390/biochem5010001
APA StylePhillips, M. J. A., Ung, A. T., Harry, E. J., Ashmore, J., & McDonagh, A. M. (2025). Synthesis and Investigation of Tricyclic Isoquinoline Derivatives as Antibacterial Agents. BioChem, 5(1), 1. https://doi.org/10.3390/biochem5010001