Substitution to Position Number 2 of 4(3H)-Quinazolinone to Create New Derivatives and to Test the Antibacterial or Antifungal Effects
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Synthesis of 2-methyl-3-p-substitutedphenyl-4(3H)-quinazolinone (1a–d)
2.2.2. Synthesis of 2-dibromomethyl-3-p-substitutedphenyl-4(3H)-quinazolinone (2a–d)
2.2.3. Synthesis of 2-disubstitutedmethyl-3-p-substitutedphenyl-4(3H)-quinazolinone (3a–s)
2.2.4. Testing of the Antifungal and Antibacterial Effects
2.2.5. Determination of the MIC of Those Derivatives with Antifungal Antibacterial Effects
3. Results
3.1. Synthesis of 4(3H)-quinazolinone
3.1.1. Synthesis of 2-methyl-3-p-substitutedphenyl-4(3H)-quinazolinone (1a–d)
3.1.2. Synthesis of 2-dibromomethyl-3-p-substitutedphenyl-4(3H)-quinazolinone (2a–d)
3.1.3. Synthesis of 2-disubstitutedmethyl-3-p-substitutedphenyl-4(3H)-quinazolinone (3a–s)
3.2. Antifungal and Antibacterial Tests of the Derivatives
3.3. MIC of Derivatives with Antifungal and Antibacterial Effects
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Synthesized Quinazolinone Derivatives | 1H-NMR (DMSO, 500 MHz) |
---|---|
1a | 8.09 (dd, J = 1.5 Hz, 8 Hz, 1H, H5); 7.85–7.81 (m, 1H, H7); 7.65 (d, J = 1 Hz, 8.5 Hz, 1H, H8); 7.53–7.49 (m, 3H, H6, H2′, H6′); 7.41–7.37 (m, 2H, H3′, H5′); 2.13 (s, 3H, –CH3) |
1b | 8.09 (dd, J = 1.5 Hz, 7.75 Hz, 1H, H5); 7.86–7.82 (m, 1H, H7); 7.66–7.62 (m, 3H, H8, H3′, H5′); 7.53–7.50 (m, 3H, H6, H2′, H6′); 2.13 (s, 3H, –CH3) |
1c | 8.09 (dd, J = 1.5 Hz, 8 Hz, 1H, H5); 7.86–7.82 (m, 1H, H7); 7.78–7.75 (m, 2H, H2′, H6′); 7.66 (d, J = 7.5 Hz, 1H, H8); 7.53–7.50 (m, 1H, H6); 7.46–7.43 (m, 2H, H3′, H5′; 2.13 (s, 3H, –CH3) |
1d | 8.42–8.40 (m, 2H, H3′, H5′); 8.11 (dd, J = 1.5 Hz, 7.75 Hz, 1H, H5); 7.87–7.84 (m, 1H, H7); 7.66–7.80 (m, 2H, H2′, H6′); 7.68 (d, J = 8 Hz, 1H, H8); 7.55–7.21 (m, 1H, H6); 2.14 (s, 3H, –CH3) |
2a | 8.29–8.28 (d, J = 8 Hz, 1H, H5); 7.90–7.83 (m, 2H, H-aromatic); 7.58–7.55 (m, 1H, H7); 7.37–7.35 (m, 2H, H6, H8); 7.31–7.27 (m, 2H, H-aromatic); 6.07 (s, 1H, HCHBr2) |
2b | 8.29–8.27 (dd, J = 1.5 Hz; 7.75 Hz, 1H, H5); 7.91–7.83 (m, 2H, H-aromatic); 7.58–7.54 (m, 1H, H7); 7.37–7.35 (m, 2H, H6, H8); 7.31–7.28 (2H, H-aromatic); 6.07 (s, 1H, HCHBr2) |
2c | 8.29–8.28 (dd, J = 8 Hz, 1H, H5); 7.90–7.85 (m, 2H, H6, H8); 7.75–7.73 (d, J = 8.5 Hz, 2H, H-aromatic); 7.58–7.55 (m, 1H, H7); 7.25–7.24 (m, 1H, H-aromatic); 6.06 (s, 1H, HCHBr2) |
2d | 8.49–8.48 (m, 2H, H-aromatic); 8.30–8.29 (dd, J = 1 Hz, 7.75 Hz, 1H, H5); 7.93–7.87 (m, 2H, H-aromatic); 7.63–7.59 (m, 3H, H6, H7, H8); 6.01 (s, 1H, HCHBr2) |
3a | 8.28–8.22 (m, 2H, H2′, H6′); 7.85 (d, J = 2 Hz, 1H, H5); 7.39 (d, J = 1 Hz, 1H, H2″); 7.32–7.27 (m, 3H,H6, H7, H8); 7.06–7.03 (m, 2H, H3′, H5′); 6.94 (d, J = 3.5 Hz, 1H, H5″); 6.45 (d, J = 3.5 Hz, 1H, H4″); 5.79 (s, 1H, CH) |
3b | 7.76–7.70 (m, 2H, H2′, H6′); 7.50 (d, J = 1.5 Hz, 1H, H5); 7.35 (d, J = 1 Hz, 2H, H2″); 7.29–7.24 (m, 3H,H6, H7, H8); 7.06–7.03 (m, 2H, H3′, H5′); 6.91 (d, J = 3.5 Hz, 1H, H5″); 6.40 (d, J = 3.5 Hz, 1H, H4″); 5.49 (s, 1H, CH) |
3c | 8.02–7.96 (m, 2H, H2′, H6′); 7.85 (d, J = 4 Hz, 1H, H5″); 7.29 (d, J = 1 Hz, 1H, H5); 7.21 (d, J = 4 Hz, 1H, H3″); 7.09–7.04 (m, 3H, H6, H7, H8); 6.95–6.92 (m, 2H, H3′, H5′); 5.21 (s, 1H, CH) |
3d | 7.57–7.51 (m, 2H, H2′, H6′); 7.45 (d, J = 4 Hz, 1H, H5″); 7.25 (d, J = 1.5 Hz, 1H, H5); 7.24 (d, J = 4 Hz, 1H, H3″); 6.80–6.75 (m, 3H, H6, H7, H8); 6.62–6.59 (m, 2H, H3′, H5′); 5.29 (s, 1H, CH) |
3e | 8.25–8.22 (m, 2H, H2′, H6′); 7.85 (d, J = 1 Hz, 1H, H5); 7.30–7.27 (m, 3H, H6, H7, H8); 7.26–7.24 (m, 2H, H3′, H5′); 7.07 (d, J = 3.5 Hz, 1H, H5″); 6.53 (d, J = 3.5 Hz, 1H, H4″); 5.87 (d, J = 3 Hz, 1H, CH); 5.06 (d, J = 3.5 Hz, 1H, NH) |
3f | 8.01–7.95 (m, 2H, H2′, H6′); 7.52 (d, J = 1.5 Hz, 1H, H5); 7.06–7.01 (m, 3H, H6, H7, H8); 6.89–6.85 (m, 2H, H3′, H5′); 6.59 (d, J = 4 Hz, 1H, H5″); 6.02 (d, J = 4 Hz, 1H, H4″); 5.31 (d, J = 2 Hz, 2H, NH); 4.87 (t, 1H, CH) |
3g | 8.69 (d, J = 5 Hz, 1H, H5′); 7.99 (d, J = 1 Hz, 1H, H2″); 7.61–7.56 (m, 3H, H6, H7, H8); 7.36–7.30 (m, 2H, H2′, H6′); 7.28–7.25 (m, 2H, H3′, H5′); 6.92 (d, J = 3.5 Hz, 1H, H5″); 6.70 (d, J = 3.5 Hz, 1H, H4″); 4.91 (s, 1H, CH) |
3h | 8.10 (d, J = 5 Hz, 1H, H5′); 7.70 (d, J = 1 Hz, 1H, H2″); 7.49–7.45 (m, 3H, H6, H7, H8); 7.44–7.29 (m, 2H, H2′, H6′); 7.27–7.24 (m, 2H, H3′, H5′); 7.04 (d, J = 3.5 Hz, 1H, H5″); 6.71 (d, J= 3.5 Hz, 1H, H4″); 4.90 (s, 1H, CH) |
3i | 7.97 (d, J = 3.5 Hz, 1H, H5″); 7.54 (d, J = 5 Hz, 1H, H5); 7.46 (d, J = 3.5 Hz, 1H, H3″); 7.29–7.24 (m, 3H, H6, H7, H8); 6.95–6.89 (m, 2H, H2′, H6′); 6.62–6.59 (m, 2H, H3′, H5′); 4.91 (s, 1H, CH) |
3j | 7.99 (d, J = 4 Hz, 1H, H5″); 7.66 (d, J = 5.5 Hz, 1H, H5); 7.47 (d, J = 4 Hz, 1H, H3″); 7.30–7.25 (m, 3H, H6, H7, H8); 6.86–6.80 (m, 2H, H2′, H6′); 6.60–6.57 (m, 2H, H3′, H5′); 4.91 (s, 1H, CH) |
3k | 7.82 (d, J = 4 Hz, 1H, H5″); 7.51 (d, J = 5 Hz, 1H, H5); 7.44 (d, J = 4 Hz, 1H, H3″); 7.27–7.22 (m, 3H, H6, H7, H8); 6.86–6.80 (m, 2H, H2′, H6′); 6.60–6.57 (m, 2H, H3′, H5′); 4.09 (s, 1H, CH) |
3l | 8.68 (d, J = 5 Hz, 1H, H5); 8.05 (d, J = 1 Hz, 2H, H2″); 7.63–7.58 (m, 3H, H6, H7, H8); 7.41–7.37 (m, 2H, H2′, H6′); 7.35–7.25 (m, 2H, H3′, H5′); 6.95 (d, J = 3.5 Hz, 1H, H5″); 6.74 (d, J = 3.5 Hz, 1H, H4″); 4.07 (s, 1H, CH) |
3n | 8.26–8.56 (m, 2H, H2′, H6′); 7.97 (d, J = 1.5 Hz, 1H, H5); 7.61 (d, J = 1 Hz, 1H, H2″); 7.39–7.34 (m, 3H, H6, H7, H8); 7.24–7.21 (m, 2H, H3′, H5′); 6.95 (d, J = 3.5 Hz, 1H, H5″); 6.46 (d, J = 3.5 Hz, 1H, H4″); 5.70 (s, 1H, CH) |
3m | 8.16 (d, J = 1.5 Hz, 1H, H5); 7.87 (d, J = 1 Hz, 2H, H2″); 7.36–7.31 (m, 3H, H6, H7, H8); 7.19–7.10 (m, 4H, H2′, H6′, H3′, H5′); 6.91 (d, J = 3.5 Hz, 1H, H5″); 6.70 (d, J = 3.5 Hz, 1H, H4″); 5.27 (s, 1H, CH) |
3o | 8.31–8. 25 (m, 2H, H2′, H6′); 7.82 (d, J = 4.5 Hz, 1H, H5″); 7.40 (d, J = 1.5 Hz, 1H, H5); 7.38 (d, J = 4.5 Hz, 1H, H3″); 7.26–7.21 (m, 3H, H6, H7, H8); 7.19–7.16 (m, 2H, H3′, H5′); 4.93 (s, 1H, CH) |
3p | 8.03 (d, J = 4.5 Hz, 2H, H5″); 8.02–7.96 (m, 2H, H2′, H6′); 7.30 (d, J = 1.5 Hz, 1H, H5); 7.26 (d, J = 4.5 Hz, 2H, H3″); 7.17–7.12 (m, 3H, H6, H7, H8); 7.04–7.01 (m, 2H, H3′, H5′); 5.21 (s, 1H, CH) |
3q | 8.25–8.19 (m, 2H, H2′, H6′); 7.84 (d, J = 1 Hz, 1H, H5); 7.30–7.25 (m, 3H, H6, H7, H8); 7.17–7.14 (m, 2H, H3′, H5′); 7.02 (d, J = 3.5 Hz, 1H, H5″); 6.49 (d, J = 3.5 Hz, 1H, H4″); 5.78 (d, J = 4 Hz, 1H, CH); 4.92 (d, J = 4.5 Hz, 1H, NH) |
3r | 8.05–8.02 (m, 2H, H3′, H5′); 7.90 (d, J = 1.5 Hz, 1H, H5); 7.64 (d, J = 1 Hz, 1H, H2″); 7.63–7.57 (m, 2H, H2′, H6′); 7.56–7.51 (m, 3H, H6, H7, H8); 6.96 (d, J = 3.5 Hz, 1H, H5″); 6.48 (d, J = 3.5 Hz, 1H, H4″); 5.32 (s, 1H, CH) |
3s | 8.04–8.01 (m, 2H, H3′, H5′); 7.89 (d, J = 1.5 Hz, 1H, H5); 7.63 (d, J = 1 Hz, 1H, H2″); 7.60–7.54 (m, 2H, H2′, H6′); 7.53–7.48 (m, 3H, H6, H7, H8); 6.92 (d, J = 3.5 Hz, 1H, H5″); 6.45 (d, J = 3.5 Hz, 1H, H4″); 5.38 (s, 1H, CH) |
References
- WHO. Antimicrobial Resistance, 17 November 2021. Available online: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed on 4 January 2022).
- WHO. New Report Calls for Urgent Action to Avert Antimicrobial Resistance Crisis, 29 April 2019. Available online: https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis (accessed on 4 January 2022).
- WHO. Antimicrobial Resistance: No Action Today, No Cure Tomorrow, 7 April 2011. Available online: https://www.who.int/director-general/speeches/detail/antimicrobial-resistance-no-action-today-no-cure-tomorrow (accessed on 4 January 2022).
- Ingle, R.G.; Magar, D.D. Heterocyclic chemistry of benzimidazoles and potential activities of derivatives. Int. J. Drug Res. Technol. 2011, 1, 26–32. [Google Scholar]
- Mahato, A.K.; Srivastava, B.; Nithya, S. Chemistry, structure activity relationship and biological activity of quinazoline-4 (3H)-one derivatives. Inventig. Rapid. Med. Chem. 2011, 2, 13–19. [Google Scholar]
- Meyer, J.F.; Wagner, E.C. The Niementowski reaction. The use of methyl anthranilate or isatoic anhydride with substituted amides or amidines in the formation of 3-substituted-4-keto-3, 4-dihydroquinazolines. The course of the reaction. J. Org. Chem. 1943, 8, 239–252. [Google Scholar] [CrossRef]
- Philipova, I.; Dobrikov, G.; Krumova, K.; Kaneti, J. Convenient synthesis of some 2-substituted 4(3H)-quinazolinone derivatives. J. Heterocycl. Chem. 2006, 43, 1057–1063. [Google Scholar] [CrossRef]
- Kidwai, M.; Rastogi, S.; Mohan, R. A Novel Route to the Niementowski Reaction. Croat. Chem. Acta 2003, 76, 365–369. [Google Scholar]
- Cheng, C.; Yan, S. The Friedländer Synthesis of Quinolines. Org. React. 2004, 28, 37–201. [Google Scholar]
- Kacker, I.K.; Zaheer, S.H. Synthesis of substituted 4-quinazolones. J. Indian Chem. Soc. 1951, 28, 344–346. [Google Scholar]
- Katritzky, A.R.; Rees, C.W.; Scriven, E.F. Comprehensive Heterocyclic Chemistry II; Pergamon: Oxford, UK, 1996. [Google Scholar]
- Furniss, B.S. Vogel's Textbook of Practical Organic Chemistry; Pearson Education India: London, UK, 1989. [Google Scholar]
- Eicher, T.; Hauptmann, S.; Speicher, A. The Chemistry of Heterocycles: Structures, Reactions, Synthesis, and Applications; John Wiley & Sons: Hoboken, NJ, USA, 2013. [Google Scholar]
- Rodriguez-Tudela, J.L.; Barchiesi, F.; Bille, J.; Chryssanthou, E.; Cuenca-Estrella, M.; Denning, D.; Verweij, P.E. Method for the determination of minimum inhibitory concentration (MIC) by broth dilution of fermentative yeasts. Clin. Microbiol. Infect. 2003, 9, i–viii. [Google Scholar] [CrossRef] [Green Version]
- Andrews, J.M. The development of the BSAC standardized method of disc diffusion testing. J. Antimicrob. Chemother. 2001, 48 (Suppl. 1), 29–42. [Google Scholar]
- CLSI. Performance Standards for Antimicrobial Susceptibility Testing, 30th ed.; CLSI supplement M100; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2020. [Google Scholar]
- Schwalbe, R.; Steele-Moore, L.; Goodwin, A.C. (Eds.) Antimicrobial Susceptibility Testing Protocols; CRC Press: Boca Raton, FL, USA, 2007. [Google Scholar]
- MacGowan, A.P.; Wise, R. Establishing MIC breakpoints and the interpretation of in vitro susceptibility tests. J. Antimicrob. Chemother. 2001, 48 (Suppl. 1), 17–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walsh, C. Antibiotics: Actions, Origins, Resistance; American Society for Microbiology (ASM) Press: Washington, DC, USA, 2003. [Google Scholar]
- Schanker, L.S. Mechanisms of drug absorption and distribution. Annu. Rev. Pharmacol. 1961, 1, 29–45. [Google Scholar] [CrossRef]
- Epand, R.M.; Epand, R.F. Bacterial membrane lipids in the action of antimicrobial agents. J. Pept. Sci. 2011, 17, 298–305. [Google Scholar] [CrossRef] [PubMed]
X = F 1a | X = Cl 1b | X = Br 1c | X = NO2 1d | |
---|---|---|---|---|
Efficiency (%) | 75 | 80 | 78 | 84 |
Characteristic | White amorphous crystals | Ivory white amorphous crystals | Ivory white scale-shaped crystals | Light blue amorphous crystals |
Melting point (°C) | 150–151 | 138–139 | 149–151 | 170–171 |
Thin-layer chromatography (Rf) | DCM–AcOEt (4:1): 0.71 n-Hex–aceton (5:2): 0.83 n-Hex–AcOEt (7:3): 0.79 | Similar to 1a | Similar to 1a | Similar to 1a |
1H-NMR (DMSO, 500 MHz) | Appendix A | Appendix A | Appendix A | Appendix A |
X = F 2a | X = Cl 2b | X = Br 2c | X = NO2 2d | |
---|---|---|---|---|
Efficiency (%) | 60 | 70 | 68 | 80 |
Characteristic | White needle-shaped crystals | White amorphous crystals | White cubic crystals | Light yellow amorphous crystals |
Melting point (oC) | 193–194 | 204–205 | 207–208 | 220–221 |
Thin-layer chromatography (Rf) | DCM–AcOEt (4:1): 0.55 n-Hex–aceton (5:2): 0.67 n-Hex–AcOEt (7:3): 0.65 | Similar to 2a | Similar to 2a | Similar to 2a |
1H-NMR (DMSO, 500 MHz) | Appendix A | Appendix A | Appendix A | Appendix A |
X, R1, R2 | Name/Symbol | Effici-ency (%) | Character-istic | Melting Point (°C) | Thin-Layer Chromatography (Rf) | 1H-NMR (DMSO, 500 MHz) | IR (cm–1) | MS |
---|---|---|---|---|---|---|---|---|
X = F, R1 = Br, R2 = Imi | 2-(bromo-(1H-imidazol-1-yl)methyl)-3-(p-fluorophenyl-4(3H)-quinazolinone (3a) | 40 | Ivory white amorphous powder | 119–120 | DCM–AcOEt (4:1): 0.28 n-Hex–aceton (5:2): 0.32 n-Hex–AcOEt (7:3): 0.30 | Appendix A (Figure S1A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S1B) | 399.21 (Figure S1C) |
X = F, R1 = R2 = Imi | 2-(di(1H-imidazol-1-yl)methyl)-3-(p-fluorophenyl-4(3H)-quinazolinone (3b) | 55 | White needle-shaped crystals | 120–121 | DCM–AcOEt (4:1): 0.38 n-Hex–aceton (5:2): 0.54 n-Hex–AcOEt (7:3): 0.50 | Appendix A (Figure S2A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S2B) | 386.27 (Figure S2C) |
X = F, R1 = Br, R2 = Tri | 2-(bromo-(1H-triazol-1-yl)methyl)-3-(p-fluorophenyl-4(3H)-quinazolinone (3c) | 35 | White needle-shaped crystals | 170–171 | DCM–AcOEt (4:1): 0.30 n-Hex–aceton (5:2): 0.34 n-Hex–AcOEt (7:3): 0.40 | Appendix A (Figure S3A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S3B) | 399.27 (Figure S3C) |
X = F, R1 = R2 = Tri | 2-(di(1H-triazol-1-yl)methyl)-3-(p-fluorophenyl-4(3H)- quinazolinone (3d) | 62 | Light gray needle-shaped crystals | 118–119 | DCM–AcOEt (4:1): 0.40 n-Hex–aceton (5:2): 0.60 n-Hex–AcOEt (7:3): 0.58 | Appendix A (Figure S4A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S4B) | 388.24 (Figure S4C) |
X = F, R1 = Br, R2 = Thi | 2-(bromo-(thiazol-2-ylamino)methyl)-3-(p-fluorophenyl-4(3H)-quinazolinone (3e) | 30 | Light orange needle-shaped crystals | 119–120 | DCM–AcOEt (4:1): 0.28 n-Hex–aceton (5:2): 0.32 n-Hex–AcOEt (7:3): 0.30 | Appendix A (Figure S5A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S5B) | 429.99 (Figure S5C) |
X = F, R1 = R2 = Thi | 2-(di(thiazol-1-ylamino)methyl)-3-(p-fluorophenyl-4(3H)-quinazolinone (3f) | 60 | Brown amorphous powder | 182–183 | DCM–AcOEt (4:1): 0.37 n-Hex–aceton (5:2): 0.61 n-Hex–AcOEt (7:3): 0.52 | Appendix A (Figure S6A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S6B) | 450.35 (Figure S6C) |
X = Cl, R1 = Br, R2 = Imi | 2-(bromo-(1H-imidazol-1-yl)methyl)-3-(p-clorophenyl-4(3H)-quinazolinone (3g) | 40 | Ivory white amorphous powder | 129–131 | DCM-AcOEt (4:1): 0.28 n-Hex–aceton (5:2): 0.32 n-Hex–AcOEt (7:3): 0.30 | Appendix A (Figure S7A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S7B) | 413.38 (Figure S7C) |
X = Cl, R1 = R2 = Imi | 2-(di(1H-imidazol-1-yl)methyl)-3-(p-clorophenyl-4(3H)-quinazolinone (3h) | 55 | Pale orange scale-shaped crystals | 144–145 | DCM–AcOEt (4:1): 0.38 n-Hex–aceton (5:2): 0.54 n-Hex–AcOEt (7:3): 0.50 | Appendix A (Figure S8A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S8B) | 402.22 (Figure S8C) |
X=Cl, R1=Br, R2=Tri | 2-(bromo-(1H-triazol-1-yl)methyl)-3-(p-clorophenyl-4(3H)-quinazolinone (3i) | 35 | White scale-shaped crystals | 109–110 | DCM–AcOEt (4:1): 0.30 n-Hex–aceton (5:2): 0.34 n-Hex–AcOEt (7:3): 0.40 | Appendix A (Figure S9A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S9B) | 415.18 (Figure S9C) |
X = Cl, R1 = R2 = Tri | 2-(di(1H-triazol-1-yl)methyl)-3-(p—clorophenyl-4(3H)-quinazolinone (3j) | 62 | Light yellow scale-shaped crystals | 144–145 | DCM–AcOEt (4:1): 0.40 n-Hex–aceton (5:2): 0.60 n-Hex–AcOEt (7:3): 0.58 | Appendix A (Figure S10A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S10B) | 304.37 (Figure S10C) |
X = Cl, R1 = H, R2 = Imi | 2-((triazol-1-yl)methyl)-3-(p-clorophenyl-4(3H)-quinazolinone (3k) | 90 | Ivory white scale-shaped crystals | 145–146 | DCM–AcOEt (4:1): 0.52 n-Hex–aceton (5:2): 0.65 n-Hex–AcOEt (7:3): 0.60 | Appendix A (Figure S11A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S11B) | 337.22 (Figure S11C) |
X=Cl, R1=H, R2=Tri | 2-((imidazol-1-yl)methyl)-3-(p-clorophenyl-4(3H)-quinazolinone (3l) | 90 | Ivory white scale-shaped crystals | 145–146 | DCM–AcOEt (4:1): 0.52 n-Hex–aceton (5:2): 0.65 n-Hex–AcOEt (7:3): 0.60 | Appendix A (Figure S12A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S12B) | 336.78 (Figure S12C) |
X = Br, R1 = Br, R2 = Imi | 2-(bromo-(1H-imidazol-1-yl)methyl)-3-(p-bromophenyl-4(3H)-quinazolinone (3n) | 55 | Ivory white scale-shaped crystals | 158–159 | DCM–AcOEt (4:1): 0.38 n-Hex–aceton (5:2): 0.54 n-Hex–AcOEt (7:3): 0.50 | Appendix A (Figure S13A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S13B) | 447.12 (Figure S13C) |
X = Br, R1 = R2 = Imi | 2-(di(1H-imidazol-1-yl)methyl)-3-(p-bromophenyl-4(3H)-quinazolinone (3m) | 40 | Ivory white amorphous powder | 135–136 | DCM–AcOEt (4:1): 0.28 n-Hex–aceton (5:2): 0.32 n-Hex–AcOEt (7:3): 0.30 | Appendix A (Figure S14A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S14B) | 457.13 (Figure S14C) |
X = Br, R1 = Br, R2 = Tri | 2-(bromo-(1H-triazol-1-yl)methyl)-3-(p-bromophenyl-4(3H)-quinazolinone (3o) | 35 | Light gray amorphous powder | 146–147 | DCM–AcOEt (4:1): 0.30 n-Hex–aceton (5:2): 0.34 n-Hex–AcOEt (7:3): 0.40 | Appendix A (Figure S15A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S15B) | 458.18 (Figure S15C) |
X = Br, R1 = R2 = Tri | 2-(di(1H-triazol-1-yl)methyl)-3-(p-bromophenyl-4(3H)-quinazolinone (3p) | 62 | Ivory white needle-shaped crystals | 159–160 | DCM–AcOEt (4:1): 0.40 n-Hex–aceton (5:2): 0.60 n-Hex–AcOEt (7:3): 0.58 | Appendix A (Figure S16A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S16B) | 448.22 (Figure S16C) |
X = Br, R1 = Br, R2 = Thi | 2-(bromo-(thiazol-2-ylamino)methyl)-3-(p-bromophenyl-4(3H)-quinazolinone (3q) | 60 | Organge amorphous powder | 165–166 | DCM–AcOEt (4:1): 0.28 n-Hex–aceton (5:2): 0.32 n-Hex–AcOEt (7:3): 0.30 | Appendix A (Figure S17A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S17B) | 489.20 (Figure S17C) |
X = NO2, R1 = Br, R2 = Imi | 2-(bromo-(1H-imidazol-1-yl)methyl)-3-(p-nitrophenyl-4(3H)-quinazolinone (3r) | 40 | Yellow needle-shaped crystals | 142–143 | DCM–AcOEt (4:1): 0.28 n-Hex–aceton (5:2): 0.32 n-Hex–AcOEt (7:3): 0.30 | Appendix A (Figure S18A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S18B) | 425.31 (Figure S18C) |
X = NO2, R1 = R2 = Imi | 2-(di(1H-imidazol-1-yl)methyl)-3-(p-nitrophenyl-4(3H)-quinazolinone (3s) | 55 | Yellow needle-shaped crystals | 170–171 | DCM–AcOEt (4:1): 0.38 n-Hex–aceton (5:2): 0.54 n-Hex–AcOEt (7:3): 0.50 | Appendix A (Figure S19A) | 1635 (C=O), 1610 (C=C), 1579 (C=N), 746 (aren) (Figure S19B) | 413.37 (Figure S19C) |
Derivatives | C. albicans | A. niger | P. aeruginosa | MRSA | B. subtilis | S. faecalis | S. aureus | E. coli |
---|---|---|---|---|---|---|---|---|
3a | - | - | - | - | - | - | - | - |
3b | - | - | - | - | - | - | - | - |
3c | - | - | - | - | - | - | - | - |
3d | - | - | - | - | - | - | + | - |
3e | - | - | - | - | - | + | - | - |
3f | + | + | + | + | - | + | + | + |
3g | - | - | - | - | - | - | + | - |
3h | - | - | - | - | - | - | + | - |
3i | - | - | - | - | - | - | + | - |
3j | - | + | - | - | - | - | + | - |
3k | - | - | - | - | - | - | + | - |
3l | - | - | - | - | - | - | - | - |
3m | - | - | - | - | - | + | + | + |
3n | - | - | - | - | - | - | - | - |
3o | - | - | - | - | - | - | - | + |
3p | - | - | - | + | - | - | + | - |
3q | - | - | - | - | - | + | + | + |
3r | - | - | - | + | - | + | + | - |
3s | - | + | - | + | - | + | + | + |
DMSO | - | - | - | - | - | - | - | - |
Derivatives | C. albicans | A. niger | P. aeruginosa | MRSA | S. faecalis | S. aureus | E. coli |
---|---|---|---|---|---|---|---|
3d | - | - | - | - | - | 256 | - |
3e | - | - | - | - | 256 | - | - |
3f | 8 | 32 | >1024 | 32 | 128 | 32 | 32 |
3g | - | - | - | - | - | >1024 | - |
3h | - | - | - | - | - | 64 | - |
3i | - | - | - | - | - | >1024 | - |
3j | - | 32 | - | - | - | 1024 | - |
3k | - | - | - | - | - | 512 | - |
3m | - | - | - | - | 256 | 256 | 256 |
3o | - | - | - | - | - | - | 1024 |
3p | - | - | - | >1024 | - | 16 | - |
3q | - | - | - | - | 256 | 256 | >1024 |
3r | - | - | - | 32 | 256 | 32 | - |
3s | - | 64 | - | 1024 | 1024 | 256 | 256 |
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Tran, H.T.; Vu, O.N.T.; Le, T.N.T.; Nguyen, B.D.C.; Vo, N.N. Substitution to Position Number 2 of 4(3H)-Quinazolinone to Create New Derivatives and to Test the Antibacterial or Antifungal Effects. Appl. Sci. 2022, 12, 2710. https://doi.org/10.3390/app12052710
Tran HT, Vu ONT, Le TNT, Nguyen BDC, Vo NN. Substitution to Position Number 2 of 4(3H)-Quinazolinone to Create New Derivatives and to Test the Antibacterial or Antifungal Effects. Applied Sciences. 2022; 12(5):2710. https://doi.org/10.3390/app12052710
Chicago/Turabian StyleTran, Huu Tam, Oanh Nhu Thi Vu, Thuy Nhu Thi Le, Bao Dam Chau Nguyen, and Ngoc Nguyen Vo. 2022. "Substitution to Position Number 2 of 4(3H)-Quinazolinone to Create New Derivatives and to Test the Antibacterial or Antifungal Effects" Applied Sciences 12, no. 5: 2710. https://doi.org/10.3390/app12052710
APA StyleTran, H. T., Vu, O. N. T., Le, T. N. T., Nguyen, B. D. C., & Vo, N. N. (2022). Substitution to Position Number 2 of 4(3H)-Quinazolinone to Create New Derivatives and to Test the Antibacterial or Antifungal Effects. Applied Sciences, 12(5), 2710. https://doi.org/10.3390/app12052710