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Current Indian Science


ISSN (Print): 2210-299X
ISSN (Online): 2210-3007

Research Article

Design, Synthesis and Antimicrobial Activity of 1,3-Diazine Derivatives

Author(s): Pranali A. Jadhav*, Jayashree R. Jagtap*, Meenakshi N. Deodhar, Rajashri S. Chavan and Smita J. Pawar

Volume 1, 2023

Published on: 01 August, 2023

Article ID: e150523216888 Pages: 15

DOI: 10.2174/2210299X01666230515090431



Background: Pyrimidines have been shown to possess numerous biological activities, such as antimicrobial, anticancer, anticonvulsant, antiviral, and antiinflammatory.

Objective: Encouraged by these data, the synthesis of 2-((1H-benzo[d]imidazol-2-yl)methylthio)-4- amino-6-phenylpyrimidine-5-carbonitrile (3a-g) was performed.

Methods: 4-amino-2-mercapto-6-phenylpyrimidine-5-carbonitrile was dissolved in an aqueous sodium hydroxide solution, and to this clear solution, 2- chloromethyl-1H-benzimidazole in methanol was added, and the reaction mixture was stirred under reflux to get the desired product. The structures of the newly synthesized compounds were confirmed by their physical, chemical, and spectral data. The synthesized derivatives were screened for their in vitro antibacterial activity against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, by using ciprofloxacin as a reference standard. While, their antifungal activity was evaluated against Aspergillus niger and Candida albicans using fluconazole as a reference drug. The docking study was performed to check the interactions of target compounds (3a-g) with homo sapiens DHFR (PDB: 1S3V), bacterial (S. aureus) DHFR (PDB: 2W9T), and DHPS (PDB: 1AD4) protein. The dock score and binding interactions were recorded.

Results: The antimicrobial activity study indicated compounds with chloro (3b), fluoro (3f), and bromo (3g) substituents to show good antibacterial as well as antifungal activity. The docking study revealed that the same compounds, i.e., 3b, 3f, and 3g, showed good dock score and comparable interactions compared to the reference ligand (trimethoprim/sulfadiazine), which confirmed their selectivity.

Conclusion: It can be presumed that the synthesized compounds have the capability for further promotion as novel antimicrobial agents.

Keywords: Antimicrobial, Pyrimidine, Antibacterial, Docking, DHFR, DHPS.

MacGowan, A.; Macnaughton, E. Antibiotic resistance. Medicine (Abingdon), 2017, 45(10), 622-628.
Verma, V.; Joshi, C.P.; Agarwal, A.; Soni, S.; Kataria, U. A Review on pharmacological aspects of pyrimidine derivatives. J. Drug Deliv. Ther., 2020, 10(5), 358-361.
Natarajan, R.; Anthoni Samy, H.N.; Sivaperuman, A.; Subramani, A.; Subramani, A. Structure-activity relationships of pyrimidine derivatives and their biological activity - a review. Med. Chem., 2022, 19(1), 10-30.
[PMID: 35579151]
Song, M.; Zhao, W.; Zhu, Y.; Liu, W.; Deng, X.; Huang, Y. Design, synthesis, and evaluation of anticonvulsant activities of new triazolopyrimidine derivatives. Front Chem., 2022, 10, 925281.
[] [PMID: 35815216]
Severina, H.; Skupa, O.O.; Voloshchuk, N.I.; Suleiman, M.M.; Georgiyants, V.A. Synthesis and anticonvulsant activity of 6-methyl-2-((2-oxo-2-arylethyl)thio)pyrimidin-4(3 H)-one derivatives and products of their cyclization. Pharmacia, 2019, 66(3), 141-146.
Provenzani, R.; San-Martin-Galindo, P.; Hassan, G.; Legehar, A.; Kallio, A.; Xhaard, H.; Fallarero, A.; Yli-Kauhaluoma, J. Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus. Sci. Rep., 2021, 11(1), 7931.
[] [PMID: 33846401]
Mahapatra, A.; Prasad, T.; Sharma, T. Pyrimidine: A review on anticancer activity with key emphasis on SAR. Future J Pharma Sci, 2021, 7(1), 123.
Tylińska, B.; Wiatrak, B.; Czyżnikowska, Ż.; Cieśla-Niechwiadowicz, A.; Gębarowska, E.; Janicka-Kłos, A. Novel pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation and molecular docking study. Int. J. Mol. Sci., 2021, 22(8), 3825.
[] [PMID: 33917090]
Jadhav, P.A.; Baravkar, A. Recent advances in antimicrobial activity of pyrimidines: A review. Asian J. Pharm. Clin. Res., 2021, 15(2), 4-10.
Tolba, M.S.; El-Dean, A.M.K.; Ahmed, M.; Hassanien, R.; Sayed, M.; Zaki, R.M.; Mohamed, S.K.; Zawam, S.A.; Abdel-Raheem, S.A.A. Synthesis, reactions, and applications of pyrimidine derivatives. Curr Chem Lett, 2022, 11(1), 121-138.
Raimondi, M.; Randazzo, O.; La Franca, M.; Barone, G.; Vignoni, E.; Rossi, D.; Collina, S. DHFR inhibitors: Reading the past for discovering novel anticancer agents. Molecules, 2019, 24(6), 1140.
[] [PMID: 30909399]
Abd El-Aleam, R.H.; George, R.F.; Hassan, G.S.; Abdel-Rahman, H.M. Synthesis of 1,2,4-triazolo[1,5-a]pyrimidine derivatives: Antimicrobial activity, DNA Gyrase inhibition and molecular docking. Bioorg. Chem., 2020, 94, 103411.
[] [PMID: 31711767]
Panneerselvam, T.; Mandhadi, J.R. Microwave assisted synthesis and antimicrobial evaluation of novel substituted thiosemicarbazide derivatives of pyrimidine. J. Heterocycl. Chem., 2020, 57(8), 3082-3088.
Al-Juboori, S.B.; Mahmood, A.A.R. Synthesis, antimicrobial evaluation, density functional theory, and docking studies of some new 2-mercapto pyrimidine schiff bases. Asian J. Pharm. Clin. Res., 2019, 12(2), 496-502.
Khatri, T.T.; Shah, V.H. Effective microwave synthesis of bioactive thieno[2,3-d]pyrtmidines. J. Chil. Chem. Soc., 2017, 62(1), 3354-3358.
Shehab, W.S.; Assy, M.G.; Moustafa, H.Y.; Abdellattif, M.H.; Rahman, H.M.A. Pyrimidines as block units in heterocycles: novel synthesis of pyrimidines and condensed pyrimidine derivatives. J. Indian Chem. Soc., 2019, 16, 2451-2461.
Fernández-Villa, D.; Aguilar, M.R.; Rojo, L. Folic acid antagonists: Antimicrobial and immunomodulating mechanisms and applications. Int. J. Mol. Sci., 2019, 20(20), 4996.
[] [PMID: 31601031]
Shamshad, H.; Bakri, R.; Mirza, A.Z. Dihydrofolate reductase, thymidylate synthase, and serine hydroxy methyltransferase: Successful targets against some infectious diseases. Mol. Biol. Rep., 2022, 49(7), 6659-6691.
[] [PMID: 35253073]
He, J.; Qiao, W.; An, Q.; Yang, T.; Luo, Y. Dihydrofolate reductase inhibitors for use as antimicrobial agents. Eur. J. Med. Chem., 2020, 195, 112268.
[] [PMID: 32298876]
Hitchings, G.H.; Burchall, J.J. Inhibition of folate biosynthesis and function as a basis for chemotherapy. Adv. Enzymol. Relat. Areas Mol. Biol., 2006, 27, 417-468.
[] [PMID: 4387360]
Patil, DR; Salunkhe, SM; Deshmukh, MB; Anbhule, PV One step synthesis of 6-amino-5-cyano-4-phenyl-2-Mercapto pyrimidine using phosphorous pentoxide. Catal J, 2010, 3, 83-86.
Petkar, K.; Parekh, P.; Mehta, P.; Kumari, A.; Baro, A. Synthesis and evaluation of 2-chloromethyl-1H-benzimidazole derivatives as antifungal agents. Int. J. Pharm. Pharm. Sci., 2013, 5(2), 115-119.
Kokare, C. Pharmaceutical Microbiology Principles and Applications, 9th ed; Nirali Publication, 2013.
Vilar, S.; Cozza, G.; Moro, S. Medicinal chemistry and the molecular operating environment (MOE): Application of QSAR and molecular docking to drug discovery. Curr. Top. Med. Chem., 2008, 8(18), 1555-1572.
[] [PMID: 19075767]
Dar, A.M.; Mir, S. Molecular docking: Approaches, types, applications and basic challenges. J. Anal. Bioanal. Tech., 2017, 8(2), 1-3.
Hawser, S.; Lociuro, S.; Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol., 2006, 71(7), 941-948.
[] [PMID: 16359642]
Capasso, C.; Supuran, C.T. Sulfa and trimethoprim-like drugs – antimetabolites acting as carbonic anhydrase, dihydropteroate synthase and dihydrofolate reductase inhibitors. J. Enzyme Inhib. Med. Chem., 2014, 29(3), 379-387.
[] [PMID: 23627736]
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