Synthesis, Antibacterial and Computational Studies of New Functionalized Sulphonamide Derivatives via Tandem Amidation Catalysis
DOI:
https://doi.org/10.54536/ajmhc.v1i1.6713Keywords:
Antibacterial Activities, Catalysis, Computational Studies, Functionalized, In Vitro Studies, Sulphonamides, Synthesis, Tandem AmidationAbstract
The development of Sulphonamides is a fascinating and informative area in medicinal chemistry, its functional group has a long and rich history in organic chemistry and drug discovery. The objective of this work is to synthesize and characterize 4-methylbenzenesulphonamides derivatives using 4-methylbenzenesulphonyl chlorides and amino acids (leucine, histidine, phenylalanine, and cysteine) as precursors, then, biological studies were carried out. The FTIR spectroscopic results confirm characteristic functional group, p-disubstituted benzene, -SO2-NH2, R3N, C=O, R2NH, Amide C=O, the IH-NMR spectrum, the peaks confirm 2o amine, p- disubstituted benzene), m- disubstituted benzene), CH3-n and CH3-CO and the 13CNMR, (acetyl C=O), (C-S=O), amide C=O, (C-H), acetyl CH3, -CH3, aromatic carbons); the results of the in silico antibacterial studies disclosed that the range of the affinity of binding is between -6.3 to -8.7 kcal/mol, with the ligands interacting more positively than other investigated microbes with the staphylococcus variant’s 6xg5 receptor, while the results of the in vitro antibacterials studies showed that at 200 mg/mL, the test organisms exhibit a zone of clearance or inhibition that varies in size from 0 to 28 mm. The spectroscopic results support the proposed structures of the compounds, the synthesized compounds have significant antibacterial potency in the respective bacteria cells, as demonstrated by the in silico antibacterial studies; these findings suggest that the synthesized compounds could be used as future antibacterial agents. According to the in vitro antimicrobial investigation, the majority of the produced compounds had antibacterial properties.
Downloads
References
Ahmed, A., Channar, P. A., & Saeed, A. (2019). Synthesis of sulfonamide, amide and amine hybrid pharmacophore: An entry of a new class of carbonic anhydrase II inhibitors and evaluation of chemoinformatics and binding analysis. Bioorganic Chemistry. https://doi.org/10.1016/j.bioorg.2019.01.060
Alison, E. W., & Shannon, S. S. (2012). Copper(II)-mediated oxidative cyclization of enamides to oxazoles. Organic & Biomolecular Chemistry, 10, 3866. https://doi.org/10.1039/C2OB25310K
Apaydın, S., & Török, M. (2019). Sulfonamide derivatives as multi-target agents for complex diseases. Bioorganic & Medicinal Chemistry Letters, 29(16), 2042–2050. https://doi.org/10.1016/j.bmcl.2019.06.041
Barbaro, G., Scozzafava, A., Mastrolorenzo, A., & Supuran, C. T. (2005). Highly active antiretroviral therapy: Current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome. Current Pharmaceutical Design, 11, 1805. https://doi.org/10.2174/1381612053764869
Bernini, R., Cacchi, S., Fabrizi, G., Filisti, E., & Sferrazza, A. (2009). 3-Aroylindoles via copper-catalyzed cyclization of N-(2-iodoaryl)enaminones. Synlett, 1480. https://doi.org/10.1055/s-0029-1216742
Bhat, M. A., Imran, M., Khan, S. A., & Siddiqui, N. (2005). Biological activities of sulfonamides. Indian Journal of Pharmaceutical Sciences, 67, 151.
Cadena, M., Durso, L. M., Miller, D. N., & Wortmann, C. (2018). Tetracycline and sulfonamide antibiotic resistance genes in soils from Nebraska organic farming operations. Frontiers in Microbiology, 9, 1283. https://doi.org/10.3389/fmicb.2018.01283
Cheung, C. W., & Buchwald, S. L. (2012). Room-temperature copper(II)-catalyzed oxidative cyclization of enamides to 2,5-disubstituted oxazoles via vinylic C–H functionalization. The Journal of Organic Chemistry, 77, 7526. https://doi.org/10.1021/jo301332s
Deng, Y., Li, B., & Zhang, T. (2018). Bacteria that degrade sulfonamide antibiotics: Blind spots and emerging opportunities. Environmental Science & Technology, 52(7), 3854–3868. https://doi.org/10.1021/acs.est.7b06026
Egbujor, M. C., & Okoro, U. C. (2019). Methionine-based p-toluenesulphonamoylcarboxamide derivatives as antimicrobial and antioxidant agents: Design, synthesis, and molecular docking. Journal of Pharmaceutical Research International, 28, 1. https://doi.org/10.9734/jpri/2019/v28i130192
Egbujor, M. C., Okoro, U. C., Okafor, S., & Nwankwo, N. E. (2019). Design, synthesis and molecular docking of novel serine-based sulphonamide compounds. Indonesian American Journal of Physical Sciences, 6, 12232. https://doi.org/10.5281/zenodo.3250306
Egbujor, M. C., Nwobodo, D. C., Egwuatu, P. I., Abu, I. P., & Ezeagu, C. U. (2020). Sulphonamide drugs and Pseudomonas aeruginosa resistance: A review. International Journal of Modern Pharmaceutical Research, 4(1), 78–83.
El-Sayed, N. S., El-Bendary, E. R., El-Ashry, S., & El-Kerdawy, M. M. (2011). Synthesis and antitumor activity of new sulfonamide derivatives. European Journal of Medicinal Chemistry, 46(9), 3714–3720. https://doi.org/10.1016/j.ejmech.2011.05.037
Eshghi, H., Rahimizadeh, M. R., Zokaei, M., Eshghi, S., Tabasi, F., Faghihi, Z. E., & Kihanyan, M. (2011). Synthesis and antimicrobial activity of macrocyclic bissulfonamides. European Journal of Chemistry, 2, 47. https://doi.org/10.5155/eurjchem.2.1.47-50.260
Fier, S. P., Luo, J., & Hartwig, J. F. (2012). Copper-mediated fluorination of aryl iodides. Journal of the American Chemical Society, 134, 10795. https://doi.org/10.1021/ja304410x
Fier, S. P., Luo, J., & Hartwig, J. F. (2013). Copper-mediated fluorination of arylboronate esters. Journal of the American Chemical Society, 135, 2552. https://doi.org/10.1021/ja310909q
Gadad, A. K., Mahajanshetti, C. S., Nimbalkar, S., & Raichurkar, A. (2000). Synthesis and antibacterial activity of thiadiazole sulfonamide derivatives. European Journal of Medicinal Chemistry, 35, 853.
Garcia-Galan, M. J., Diaz-Cruz, M. S., & Barceló, D. (2008). Identification of sulfonamide antibiotic metabolites. Trends in Analytical Chemistry, 27(11), 1008–1022.
Gidden, A. C., Gamage, S. A., & Kendall, J. D. (2019). Sulfonamide analogues of PI3K inhibitor ZSTK474. Bioorganic & Medicinal Chemistry, 27(8), 1529–1545.
Ihejieto, A. I., Okoro, U. C., & Jacob, A. D. (2015). Copper-catalyzed N-arylation of angular triazaphenothiazinone. Chemistry and Materials Research, 7(4), 144–147.
Jacob, A. D., & Okoro, U. C. (2014). Copper-catalyzed arylation in synthesis of triazaphenoxazinone derivatives. Chemistry and Materials Research, 6(9), 37–40.
Jacob, A. D., Okoro, U. C., & Dauda, A. J. (2024a). Copper(I) oxide catalysis in alanine-based sulphonamides synthesis. Covenant Journal of Health and Life Sciences, 2(2), 1-12.
Jacob, A. D., Okoro, U. C., & Dauda, A. J. (2024b). Copper-catalyzed synthesis of glycine-based sulphonamides. Recent Advances in Natural Sciences, 2(1), 36. https://doi.org/10.61298/rans.2024.2.1.36
Jithunsa, M., Ueda, M., & Miyata, O. (2011). Copper(II) chloride-mediated cyclization reaction of N-alkoxy-ortho-alkynylbenzamides. Organic Letters, 13(3), 518–521. https://doi.org/10.1021/ol1029035
Karch, A. M. (2011). Focus on nursing pharmacology (5th ed.). Lippincott Williams & Wilkins.
Khanusiya, M., & Gadhawala, Z. (2019). Chalcones–sulphonamide hybrids: Synthesis, characterization and anticancer evaluation. Journal of the Korean Chemical Society, 63(2), 85–90. https://doi.org/10.5012/jkcs.2019.63.2.85
Liangbin, H., Huanfeng, J., Chaorong, Q., & Xiaohang, L. (2010). Copper-catalyzed intermolecular oxidative [3 + 2] cycloaddition between alkenes and anhydrides: A new synthetic approach to γ-lactones. Journal of the American Chemical Society, 132(50), 17652–17653. https://doi.org/10.1021/ja108073k
Ma, J., & Cahard, D. (2004). Copper(II) triflate–bis(oxazoline)-catalyzed enantioselective electrophilic fluorination of β-ketoesters. Tetrahedron: Asymmetry, 15(6), 1007–1011. https://doi.org/10.1016/j.tetasy.2004.01.014
Marealle, A. I., Mbwambo, D. P., & Mikomangwa, W. P. (2018). A decade since sulfonamide-based antimalarial medicines were limited for intermittent preventive treatment among pregnant women in Tanzania. Malaria Journal, 17, 409. https://doi.org/10.1186/s12936-018-2565-1
Onoabedje, E. A., Ibezim, A., Okoro, U. C., & Batra, S. (2021). New sulphonamide pyrrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities. PLoS ONE, 16(1), e0243305. https://doi.org/10.1371/journal.pone.0243305
Orie, K. J., Duru, R. U., & Ngochindo, R. I. (2021a). Metal complexes of heterocyclic sulphonamide: Synthesis, characterization and biological activity. Science Journal of Analytical Chemistry, 9(4), 104–110. https://doi.org/10.11648/j.sjac.20210904.14
Orie, K. J., Duru, R. U., & Ngochindo, R. I. (2021b). Synthesis and spectroscopic studies of zinc(II) and copper(II) complexes of 4-methyl-N-(pyridin-2-yl)benzene sulphonamide. World Journal of Applied Chemistry, 6(2), 19–24. https://doi.org/10.11648/j.wjac.20210602.12
Orie, K. J., Ike, C. D., & Nzeneri, J. U. (2021). Synthesis and characterization of metal complexes with 4-methyl-N-(p-methylphenylsulphonyl)-N-(pyridin-2-yl)benzene sulphonamide. Modern Chemistry, 9(3), 46–52. https://doi.org/10.11648/j.mc.20210903.11
Reddy, N. S., Rao, A. S., Chari, M. A., Kumar, V. R., Jyothy, V., & Himabindu, V. (2012). Synthesis and antibacterial activity of sulfonamide derivatives at C-8 alkyl chain of anacardic acid mixture isolated from cashew nut shell liquid (CNSL). Journal of Chemical Sciences, 124(3), 723–730. https://doi.org/10.1007/s12039-012-0253-1
Satoshi, U., & Hideko, N. (2009). Facile synthesis of 1,2,4-triazoles via a copper-catalyzed tandem addition–oxidative cyclization. Journal of the American Chemical Society, 131(42), 15080–15081. https://doi.org/10.1021/ja905056z
Sirdar, M. M., Picard, J., Bisschop, S., Jambalang, A. R., & Gummow, B. (2012). A survey of antimicrobial residues in table eggs in Khartoum State, Sudan (2007–2008). Onderstepoort Journal of Veterinary Research, 79(1), 1–9. https://doi.org/10.4102/ojvr.v79i1.360
Standley, E. A., & Jamison, T. F. (2013). Simplifying nickel(0) catalysis: An air-stable nickel precatalyst for the internally selective benzylation of terminal alkenes. Journal of the American Chemical Society, 135(5), 1585–1592. https://doi.org/10.1021/ja3116718
Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
Van den Bogaard, A., London, N., Driessen, C., & Stobberingh, E. (2001). Antibiotic resistance of faecal Escherichia coli in poultry, poultry farmers and poultry slaughterers. Journal of Antimicrobial Chemotherapy, 47(6), 763–771. https://doi.org/10.1093/jac/47.6.763
Wan, C., Zhang, J., Wang, S., Fan, J., & Wang, Z. (2010). Facile synthesis of polysubstituted oxazoles via a copper-catalyzed tandem oxidative cyclization. Organic Letters, 12(10), 2338–2341. https://doi.org/10.1021/ol100688c
Yan, J., Li, J., & Cheng, D. (2007). Mild and efficient indium metal-catalyzed synthesis of sulfonamides and sulfonic esters. Synlett, 2007(16), 2501–2504. https://doi.org/10.1055/s-2007-986632
Yoshii, D. (2019). Selective dehydrogenative mono- or diborylation of styrenes by supported copper catalysts. ACS Catalysis, 9(4), 3011–3016. https://doi.org/10.1021/acscatal.9b00761
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Alifa Jacob, Uchechukwu Okoro, Abiodun Dauda, Wisdom Oniwon, Friday Oteno, Gabriel Ocheme, Ashem Agieni, Cliford Okpanachi, Charity Ejim (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
