Synthesis and Characterization of Some New Pyrazole and Pyrimidine Derivatives From Chalcones and Evaluation of Their Biological Effectiveness
Abstract
This study includes the preparing a new series of pyrazolin and pyrimidine derivatives that are expected to have promising biological properties. The preparation process was achieved through cyclization reactions and optimized reaction conditions to ensure high purity and yield of the target compounds. The first step includes the synthesis of (E)-3-(4-aminophenyl)-1-(2-chloroquinolin-3-yl)prop-2-en-1-one (M1) from the reaction between 2-chloroquinoline-3-carbaldehyde and 1-(4-aminophenyl)ethan-1-one. The second step includes the synthesis of (E)-N-(4-(3-(2-chloroquinolin-3-yl)-3-oxoprop-1-en-1-yl)phenyl)benzamide(M2) via reaction a mixture of (E)-3-(4-aminophenyl)-1-(2-chloroquinolin-3-yl)prop-2-en-1-one (M1) and benzoyl chloride in the presence of pyridine. The third step includes the synthesis of pyrazole compounds (M3-M6) via the reaction of compounds (M2) with phenylhydrazine, hydrazine hydrate 80%, thiosemicarbazide, and hydrazine carboxamide, and finally, the production of pyrimidine compounds (M7-M8) via the condensation of compounds (M2) with thiourea and urea. The structures of the prepared compounds were confirmed using advanced analytical techniques, including (13C-NMR and 1H-NMR) spectroscopy, as well as infrared (IR) spectroscopy. These spectroscopic techniques provided detailed structural data that contributed to identifying and confirming the chemical structures of the new compounds. Furthermore, the biological activity of the prepared compounds was evaluated against a variety of microorganisms, including bacteria Escherichia coli, pseudomonas, and Staphylococcus aureus, The antibacterial activity of compounds (M3, M4, M6 and M7) showed a significant effect as inhibitors of bacterial growth, while the rest of the compounds showed a weak to moderate effect compared to antibiotics. The results of this research contribute to expanding the library of biologically important heterocyclic compounds and open new horizons for the development of potential drugs with improved efficacy and fewer side effects.
References
R. V. Patel and S. W. Park, "Access to a new class of biologically active quinoline based 1, 2, 4-triazoles," European Journal of Medicinal Chemistry, vol. 71, pp. 24-30, 2014.
S. Narwal, S. Kumar, and P. K. Verma, "Synthesis and therapeutic potential of quinoline derivatives," Research on Chemical Intermediates, vol. 43, pp. 2765-2798, 2017.
L. Feng et al., "Synthesis and in vitro antibacterial activity of gemifloxacin derivatives containing a substituted benzyloxime moiety," European journal of medicinal chemistry, vol. 55, pp. 125-136, 2012.
T. Kaur and D. D. Bhandari, "Annotated review on various biological activities of quinoline molecule," Biointerface Res. Appl. Chem, vol. 13, no. 4, p. 355, 2023.
B. Medapi et al., "Design and synthesis of novel quinoline–aminopiperidine hybrid analogues as Mycobacterium tuberculosis DNA gyraseB inhibitors," Bioorganic & medicinal chemistry, vol. 23, no. 9, pp. 2062-2078, 2015.
T. K. Köprülü, S. Ökten, V. E. Atalay, Ş. Tekin, and O. Çakmak, "Biological activity and molecular docking studies of some new quinolines as potent anticancer agents," Medical Oncology, vol. 38, no. 7, p. 84, 2021.
S. Rossiter, J.-M. Peron, P. J. Whitfield, and K. Jones, "Synthesis and anthelmintic properties of arylquinolines with activity against drug-resistant nematodes," Bioorganic & medicinal chemistry letters, vol. 15, no. 21, pp. 4806-4808, 2005.
T. A. Rano, E. Sieber-McMaster, P. D. Pelton, M. Yang, K. T. Demarest, and G.-H. Kuo, "Design and synthesis of potent inhibitors of cholesteryl ester transfer protein (CETP) exploiting a 1, 2, 3, 4-tetrahydroquinoline platform," Bioorganic & medicinal chemistry letters, vol. 19, no. 9, pp. 2456-2460, 2009.
G. Roma et al., "1, 8-Naphthyridines VII. New substituted 5-amino [1, 2, 4] triazolo [4, 3-a][1, 8] naphthyridine-6-carboxamides and their isosteric analogues, exhibiting notable anti-inflammatory and/or analgesic activities, but no acute gastrolesivity," European Journal of Medicinal Chemistry, vol. 43, no. 8, pp. 1665-1680, 2008.
H. MT Albuquerque, C. MM Santos, J. AS Cavaleiro, and A. MS Silva, "Chalcones as Versatile Synthons for the Synthesis of 5-and 6-membered Nitrogen Heterocycles," Current Organic Chemistry, vol. 18, no. 21, pp. 2750-2775, 2014.
M. J. Ahsan et al., "Pyrazoline containing compounds as therapeutic targets for neurodegenerative disorders," ACS omega, vol. 7, no. 43, pp. 38207-38245, 2022.
Z. D. Najmuldeen and T. N. Omar, "Synthesis, characterization and evaluation of new pyrazoline derivatives containing sulfonamide moiety as anti-microbial and anti-inflammatory agents," Journal of Research in Medical and Dental Science, vol. 11, no. 1, pp. 73-81, 2023.
M. R. Al-Nakeeb and T. N. Omar, "Synthesis, characterization and preliminary study of the anti-inflammatory activity of new pyrazoline containing ibuprofen derivatives," Iraqi Journal of Pharmaceutical Sciences, vol. 28, no. 1, pp. 131-137, 2019.
R. Natarajan, H. N. Anthoni Samy, A. Sivaperuman, and A. Subramani, "Structure-activity relationships of pyrimidine derivatives and their biological activity-A review," Medicinal Chemistry, vol. 19, no. 1, pp. 10-30, 2023.
M. M. Al-Tufah, S. S. Jasim, and K. A. Al-Badrany, "Synthesis and Antibacterial Evaluation of some New Pyrazole Derivatives," Prof.(Dr) RK Sharma, vol. 20, no. 3, p. 178, 2020.
T. P. Selvam, C. R. James, P. V. Dniandev, and S. K. Valzita, "A mini review of pyrimidine and fused pyrimidine marketed drugs," Research in Pharmacy, vol. 2, no. 4, 2015.
A. Kumar et al., "Nitrogen containing heterocycles as anticancer agents: A medicinal chemistry perspective," Pharmaceuticals, vol. 16, no. 2, p. 299, 2023.
S. Vega, J. Alonso, J. A. Diaz, and F. Junquera, "Synthesis of 3‐substituted‐4‐phenyl‐2‐thioxo‐1, 2, 3, 4, 5, 6, 7, 8‐octahydrobenzo [4, 5] thieno [2, 3‐á] pyrimidines," Journal of Heterocyclic Chemistry, vol. 27, no. 2, pp. 269-273, 1990.
F. Xie, H. Zhao, L. Zhao, L. Lou, and Y. Hu, "Synthesis and biological evaluation of novel 2, 4, 5-substituted pyrimidine derivatives for anticancer activity," Bioorganic & medicinal chemistry letters, vol. 19, no. 1, pp. 275-278, 2009.
N. Venkatathri, "Synthesis and characterization of high silica content silicoaluminophosphate SAPO-35 from non-aqueous medium," Catalysis Communications, vol. 7, no. 10, pp. 773-777, 2006.
A. E.-G. E. Amr, N. M. Sabry, and M. M. Abdulla, "Synthesis, reactions, and anti-inflammatory activity of heterocyclic systems fused to a thiophene moiety using citrazinic acid as synthon," Monatshefte für Chemie-Chemical Monthly, vol. 138, pp. 699-707, 2007.
L. Ballell, R. A. Field, G. A. Chung, and R. J. Young, "New thiopyrazolo [3, 4-d] pyrimidine derivatives as anti-mycobacterial agents," Bioorganic & medicinal chemistry letters, vol. 17, no. 6, pp. 1736-1740, 2007.
E. Wagner, K. Al-Kadasi, M. Zimecki, and W. Sawka-Dobrowolska, "Synthesis and pharmacological screening of derivatives of isoxazolo [4, 5-d] pyrimidine," European Journal of Medicinal Chemistry, vol. 43, no. 11, pp. 2498-2504, 2008.
M. M. Al-Tufah, S. Beebaeny, S. S. Jasim, and B. L. Mohammed, "Synthesis, characterization of ethyl dioxoisoindolinyl cyclohexenone carboxylate derivatives from some chalcones and its biological activity assessment," Chemical Methodologies, vol. 7, pp. 408-418, 2023.
M. Megawati, M. Yuwono, and R. Primaharinastiti, "Antibacterial activity of Randu Honey against some bacterial pathogens using agar well diffusion method," Riset Informasi Kesehatan, vol. 14, no. 1, pp. 49-57, 2025.
M. M. Al-Tufah and D. I. Madab, "Synthesis and Characterization of New Imidazole Derivatives and Evaluation of Biological Efficacy," American Journal of Bioscience and Clinical Integrity Volume, vol. 2, no. 3, 2025.
Copyright (c) 2025 Dhamer Ismael Madab, Mohammad M.Al- Tufah
This work is licensed under a Creative Commons Attribution 4.0 International License.
