Design, Synthesis of Some New Quinazolinone Derivatives and Evaluation of their Antibacterial Activity

Aseel Jassim  Mohammed; Oday H.R. Al-Jeilawi

doi:10.30526/38.3.3620

Authors

Aseel Jassim Mohammed Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq. https://orcid.org/0009-0000-7295-5269
Oday H.R.Al -Jeilawi Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0002-4092-2072

DOI:

https://doi.org/10.30526/38.3.3620

Keywords:

Antibacterial activity, Methyl anthranilate, Thiourea derivative, Quinazolinone derivatives

Abstract

The novel quinazolinone derivatives were synthesized in excellent yields, manufactured, characterized, and investigated for their biological activity. This study aims to produce new quinazolinone derivatives and study their antibacterial activity. Quinazolinone derivatives were synthesized in three steps: the first step included the reaction of methyl anthranilate with isothiocyanatobenzene to produce a thiourea derivative (A1). In the second step (A1) was reacted with hydrazine hydrate to synthesized 3-Amino-2-(phenylamino) quinazolin-4(3H)-one (A2). The third step consisted of the reaction of (A2) with various organic compounds (phenylisotiocyanate, phenylisocyanate, acid halide, benzyl halide, and alkyl halide derivatives) to produce new derivatives. FT-IR, ¹HNMR, and ¹³C NMR spectroscopy were used to identify the chemical structure of these compounds. The agar well diffusion technique was used to determine the antibacterial activity levels exhibited by the samples. Staphylococcus aureus and Escherichia coli were used as test organisms in this study. When compared to the antibiotic used as a standard, amikacin, these compounds demonstrated superior antibacterial activity.

Author Biographies

Aseel Jassim Mohammed, Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.

Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.
Oday H.R.Al -Jeilawi , Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.

Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.

References

1. Nief OA, Alzahawy HMG, Abdallah EK, Attia AM. Synthesis and identification of five-membered ring heterocyclic compounds derived from trimethoprim. Al Nahrain J Sci. 2018;1:1–7. https://doi.org/10.22401/ANJS.00.1.01.

2. Al Sultani KT, Al Majidi SM, Al Jeilawi OH. Synthesis, identification and evaluation biological activity for some new triazole, triazoline and tetrazoline derivatives from 2 mercapto 3 phenyl 4(3H) quinazolinone. Iraqi J Sci. 2016; 57(1B):295–308.

3. Khan I, Ibrar A, Ahmed W, Saeed A. Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: the advances continue. Eur J Med Chem. 2015; 90:124–169. https://doi.org/10.1016/j.ejmech.2014.10.084.

4. Monier M, Abdel Latif DEL M, Elattar KM. Bicyclic 6+6 systems: advances in the chemistry of heterocyclic compounds incorporated pyrimido[1,2 a]pyrimidine skeleton. Mini Rev Org Chem. 2020; 17(6):717–739. http://dx.doi.org/10.2174/1389557519666190925161145.

5. Maiden TMM, Harrity JPA. Recent developments in transition metal catalysis for quinazolinone synthesis. Org Biomol Chem. 2016;14(34):8014–8025. https://doi.org/10.1039/C6OB01402J.

6. Ranjith R. The chemistry and biological significance of imidazole, benzimidazole, benzoxazole, tetrazole and quinazolinone nucleus. J Chem Pharm Res. 2016; 8(5):505–526.

7. Lazou M, Tarushi A, Gritzapis P, Psomas G. Transition metal complexes with a novel guanine based (E) 2 (2 (pyridin 2 ylmethylene)hydrazinyl)quinazolin 4(3H) one: synthesis, characterization, interaction with DNA and albumins and antioxidant activity. J Inorg Biochem. 2020; 206:111019. https://doi.org/10.1016/j.jinorgbio.2020.111019.

8. Özturk S, Okay S, Yıldırım A. Synthesis, anticorrosion, antibacterial, and antifungal activity of new amphiphilic compounds possessing quinazolin 4(3H) one scaffold. Russ Chem Bull. 2020; 69:2205–2214. https://doi.org/10.1007/s11172-020-3023-0.

9. Wang X, Hu H, Zhao X, Chen M, Zhang T, Geng C, Mei Y, Lu A, Yang C. Novel quinazolin 4(3H) one derivatives containing a 1,3,4 oxadiazole thioether moiety as potential bactericides and fungicides: design, synthesis, characterization and 3D QSAR analysis. J Saudi Chem Soc. 2019; 23(8):1144–1156. https://doi.org/10.1016/j.jscs.2019.07.006.

10. Al Jeilawi OH, Al Ani HN, Al Zahra A, Al Sultani KT. Exploring the potential of quantum chemical calculations for synthesized quinazoline derivatives as superior corrosion inhibitors in acidic environment. Phys Chem Res. 2024;12(1):205–217. https://doi.org/10.22036/pcr.2023.390388.2314.

11. Al Zahra A, Al Ani HN, Al Jeilawi OH. Experimental and theoretical study of 3-benzyl-2- mercaptoquinazolin 4(3H) one (BMQ) as an inhibitor of carbon steel corrosion in acidic media. Int J Sci Nutral. 2018; 9(1):105–113.

12. Xing Z, Wu W, Miao Y, Tang Y, Zhou Y, Zheng L, Fu Y, Song Z, Peng Y. Recent advances in quinazolinones as an emerging molecular platform for luminescent materials and bioimaging. Org Chem Front. 2021; 8(8):1867–1889. https://doi.org/10.1039/D0QO01425G.

13. Nguyen CT, Nguyen QT, Dao PH, Nguyen TL, Nguyen PT, Nguyen HH. Synthesis and cytotoxic activity against K562 and MCF 7 cell lines of some N (5 arylidene 4 oxo 2 thioxothiazolidin 3 yl) 2 ((4 oxo 3 phenyl 3,4 dihydroquinazoline 2 yl)thio)acetamide compounds. J Chem. 2019; 2019(2b):1–8. http://dx.doi.org/10.1155/2019/1492316.

14. Shamaya AN, Al Jeilawi OH, Khudhair NA. Novel synthesis of some N hydroxy phthalimide derivatives with investigation of its corrosion inhibition for carbon steel in HCl solution. Chem Methodol. 2021; 5(4):331–340. https://doi.org/10.22034/chemm.2021.131305.

15. Nasab RR, Karami B, Khodabakhshi S. Selective solvent free Biginelli condensation using tungstate sulfuric acid as powerful and reusable catalyst. Bull Chem React Eng Catal. 2014; 9(2):148–154. https://doi.org/10.9767/bcrec.9.2.6794.148-154.

16. Mohammadkhani L, Heravi MM. Microwave assisted synthesis of quinazolines and quinazolinones: an overview. Front Chem. 2020; 8:580086. https://doi.org/10.3389/fchem.2020.580086.

17. Karaali N. A convenient method for the synthesis of 3,4 dihydroquinazolines from iminoester hydrochlorides via microwave irradiation. J Chem Res. 2019; 43(3–4):140–143. https://doi.org/10.1177/1747519819857513.

18. Auti PS, George G, Paul AT. Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids. RSC Adv. 2020; 10(68):41353–41392. https://doi.org/10.1039/D0RA06642G.

19. Kushwaha N, Sahu A, Mishra J, Soni A, Dorwal D. An insight on the prospect of quinazoline and quinazolinone derivatives as anti tubercular agents. Curr Org Synth. 2023; 20(8):838-869.

https://doi.org/ 10.2174/1570179420666230316094435.

20. Xu M, Wu P, Shen F, Ji J, Rakesh K. Chalcone derivatives and their antibacterial activities: current development. Bioorg Chem. 2019; 91:103133. https://doi.org/10.1016/j.bioorg.2019.103133.

21. Sharma P, Sharma D, Sharma A, Saini N, Goyal R, Ola M, Chawla R, Thakur V. Hydrazone comprising compounds as promising anti infective agents: chemistry and structure property relationship. Mater Today Chem. 2020; 18:100349. https://doi.org/10.1016/j.mtchem.2020.100349.

22. Rossi R, Ciofalo M. An updated review on the synthesis and antibacterial activity of molecular hybrids and conjugates bearing imidazole moiety. Molecules. 2020; 25(21):5133. https://doi.org/ 10.3390/molecules25215133.

23. El Saadi MT, Amin NH. Synthesis, docking, and biological evaluation of 2,4-disubstituted quinazolines with multi-target activities as anti-cancer and antimicrobial agents. Egypt J Chem. 2020; 63(10):3721–3734. https://doi.org/10.21608/ejchem.2020.23300.2385.

24. Oleiwi AQ, Al Jeilawi OH, Dayl SA. Synthesis, characterization of some thiourea derivatives based on 4 methoxybenzoyl chloride as antioxidants and study of molecular docking. Iraqi J Sci. 2023; 64(1): 1–12. https://orcid.org/0000-0002-1317-8268.

25. Sayahi MH, Saghanezhad SJ, Bahadorikhalili S, Mahdavi M. CuBr catalysed one pot multicomponent synthesis of 3 substituted 2 thioxo 2,3 dihydroquinazolin 4(1H) one derivatives. Appl Organomet Chem. 2019; 33(1):e4635. http://dx.doi.org/10.1002/aoc.4635.

26. Tokalı FS, Demir Y, Demircioğlu İH, Türkeş C, Kalay E, Şendil K, Beydemir Ş. Synthesis, biological evaluation, and in silico study of novel library sulfonates containing quinazolin 4(3H) one derivatives as potential aldose reductase inhibitors. Drug Dev Res. 2022; 83(3):586–604. https://doi.org/10.1002/ddr.21887.

27. Saeed S, Hussain R. A convenient way for the preparation of novel thiourea derivatives containing biologically active quinazoline moiety. Eur Chem Bull. 2013; 2(7):465–467.

28. Bousfield TW, Pearce KP, Nyamini SB, Angelis Dimakis A, Camp JE. Synthesis of amides from acid chlorides and amines in the bio based solvent Cyrene™. Green Chem. 2019; 21(13):3675–3681. https://doi.org/10.1039/C9GC01180C.

29. Salvatore RN, Yoon CH, Jung KW. Synthesis of secondary amines. Tetrahedron. 2001; 57(37):7785–7812. http://dx.doi.org/10.1016/S0040-4020(01)00722-0.

30. Erhonyota C, Edo GI, Onoharigho FO. Comparison of poison plate and agar well diffusion method determining the antifungal activity of protein fractions. Acta Ecol Sin. 2023; 43(4):684–689.https://doi.org/10.1016/j.chnaes.2022.08.006.

31. Latheef L, Kurup MP. Synthesis and spectral studies of 3 azacyclothiosemicarbazones. J Adv Sci Res. 2019; 10(Suppl 2):333–338. https://www.sciensage.info/index.php/JASR/article/view/395.

32. Rao C, Venkataraghavan R. The C=S stretching frequency and the “–N–C=S bands” in the infrared. Spectrochim Acta A Mol Spectrosc. 1989; 45:299–305.

33. Silverstein RM, Webster FX, Kiemle DJ. Spectrometric identification of organic compounds. 7th ed. New York: John Wiley & Sons; 2005.

34. Mustafa IF, Hussain EM. Synthesis and antimicrobial evaluation of new 1,3,4 thiadiazole derivatives. IHJPAS. 2017; 27(1):297–305. https://jih.uobaghdad.edu.iq/index.php/j/article/view/395.