Synthesis and Evaluation of 1,2,3-Triazole Derivatives of Sulfamethoxazole as Potential Antimicrobial Agents
Mohammed A. Dakhil 1, Mustafa Kadhum Naeem 2, Farked Wahoodi Salman 3, Ali Jabbar Radhi 4*
Microbial Bioactives 7(1) 1-10 https://doi.org/10.25163/microbbioacts.719663
Submitted: 18 March 2024 Revised: 29 April 2024 Published: 01 May 2024
Abstract
Background: Sulfamethoxazole, a commonly used antibiotic, has faced challenges due to emerging resistant bacterial strains. Recent efforts have focused on synthesizing sulfamethoxazole derivatives incorporating 1,2,3-triazole heterocycles, known for their diverse pharmacological activities. Methods: The synthesis of azido sulfamethoxazole and its subsequent transformation into 1,2,3-triazole derivatives (1t, 2t, and 3t) were achieved through copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Characterization of synthesized compounds was performed using FT-IR and NMR spectroscopy. Antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated using the diffusion method on Mueller-Hinton agar. Molecular docking studies were conducted to predict interactions between synthesized compounds and bacterial proteins. Results: Successful synthesis of azido sulfamethoxazole and 1,2,3-triazole derivatives was confirmed through spectroscopic analyses. The derivatives exhibited promising antibacterial activity against both Gram-negative and Gram-positive bacteria, with some compounds showing synergistic effects when combined with existing antibiotics. Molecular docking studies revealed potential binding interactions between the synthesized compounds and bacterial proteins. Conclusion: The study demonstrated the effective synthesis of novel sulfamethoxazole derivatives incorporating 1,2,3-triazole heterocycles, exhibiting significant antibacterial activity.
Keywords: Antimicrobial resistance, Sulfamethoxazole derivatives, 1,2,3-Triazole heterocycles, Click chemistry, Antibacterial activity
References
Abdulah Y. Al-Mahdi, Alabed Ali A. Alabed, Mohammed Faez Baobaid et al., (2024). Antibacterial Activity of Herbal Essential Oils against Gram-positive and Gram-negative Bacteria with a Potential for Multidrug Resistance, Journal of Angiotherapy, 8(2), 1-7, 9517
Adams, R., & Johnson, M. (2018). Addressing Antibiotic Resistance: A Comprehensive Review. Journal of Medical Microbiology, 67(3), 308-318.
Alsahib, S. A. (2020). Characterization and biological activity of some new derivatives derived from sulfamethoxazole compound. Baghdad Sci. J, 17(2), 471-480.
Brown, A., & Patel, D. (2019). Structural Modification of Antibiotics: A Review. Chemical Reviews, 119(5), 3219-3270.
Chen, S., & Miller, T. (2021). Computational Approaches in Antibacterial Drug Discovery: A Review. Frontiers in Pharmacology, 12, 589739.
Chu, X. M., Wang, C., Wang, W. L., Liang, L. L., Liu, W., Gong, K. K., & Sun, K. L. (2019). Triazole derivatives and their antiplasmodial and antimalarial activities. European journal of medicinal chemistry, 166, 206-223.
El-Sayed, W. A., & Abdel-Rahman, A. A. H. (2010). Copper-catalyzed Synthesis and Antimicrobial Activity of Disubstituted 1, 2, 3-Triazoles Starting from 1-Propargyluracils and Ethyl (4-azido-1, 2, 3-trihydroxybutyl) furan-3-carboxylate. Zeitschrift für Naturforschung B, 65(1), 57-66.
Farah M. Muhammad, Bushra A. Khairallah, K. A. Albadrany. (2024). Synthesis, characterization and Antibacterial Evaluation of Novel 1,3-Oxazepine Derivatives Using A Cycloaddition Approach, Journal of Angiotherapy, 8(3), 1-5, 9506
Garcia, L., et al. (2019). Characterization Techniques in Organic Chemistry: A Comprehensive Guide. Wiley.
Garneau-Tsodikova, S., & Labby, K. J. (2016). Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives. Medchemcomm, 7(1), 11-27.
Gonder LY, Aydin B, Ates YC, Parilti DN, Acik L and Cerci A. (2023). Antimicrobial, Antioxidant, Cytotoxic, DNA Protective Activities, and Molecular Docking Studies of the Methanolic Extract of Salvia siirtica Kahraman, Celep & Dogan sp. Nov. (Lamiaceae). Microbial Bioactives, Vol. 6, Article 1.
Goud, G. L., Ramesh, S., Ashok, D., Reddy, V. P., Yogeeswari, P., Sriram, D., … & Manga, V. (2017). Design, synthesis, molecular-docking and antimycobacterial evaluation of some novel 1, 2, 3-triazolyl xanthenones. MedChemComm, 8(3), 559-570.
Green Synthetic Routes for Heterocyclic Compound Synthesis: A Review. Green Chemistry, 20(7), 1419-1437.
Gupta, S., & Lee, J. (2020). Synthetic Strategies for Heterocyclic Compound Synthesis: A Review. Organic Chemistry Frontiers, 7(4), 527-550.
HASAN, H. A., TALIB, N. T., OBAID, E. K., & RADHI, A. J. (2020). Synthesis and Identification of New Nitrogen Rich Polymers Based on Sulfa Drug Derivatives. International Journal of Pharmaceutical Research (09752366), 12(3).
Hayder Kadhim Abbas, Ehab K. Obaid, Ali Jabbar Radhi, Synthesis and Study of Biological Activities of Water-Soluble Derivatives of Metronidazole Based on Carbohydrate, Malaysian Journal of Chemistry, 2021, 23(4), 29-36.
Hiba Ahmed Jawade, Zahraa Yosif Motaweq, Hawraa Dheyaa Rasool et al. (2024). Study of Antibiotic Resistance in ESKAPE Bacteria Using β-lactamase and ESBL Genes, Journal of Angiotherapy, 8(3), 1-8, 9618
Huang, R. Z., Liang, G. B., Li, M. S., Fang, Y. L., Zhao, S. F., Zhou, M. M., … & Wang, H. S. (2019). Synthesis and discovery of asiatic acid based 1, 2, 3-triazole derivatives as antitumor agents blocking NF-κB activation and cell migration. MedChemComm, 10(4), 584-597.
Hussein Abdulkadhim Hasan, Saad M. Mahdi, Hanaa Addai Ali. (2024). Synthesis, Charecterization, Antibacterial and Cytotoxicity of Novel Metal Complexes Derived from Azomethine Ligand (Bis Azo-Schiff Base) In Vitro and In Silico, Journal of Angiotherapy, 8(3), 1-12, 9531
Jiang, X., Wu, G., Zalloum, W. A., Meuser, M. E., Dick, A., Sun, L., … & Zhan, P. (2019). Discovery of novel 1, 4-disubstituted 1, 2, 3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors. RSC advances, 9(50), 28961-28986.
Jinia Afroz, Md. Al Masud, Esrat Jahan, Ajoy Chowdhury, Md. Fakruddin, Md. Asaduzzaman Shishir, (2023), Multi-Antibiotic Resistant Citrobacter freundii in Eggs: A Silent Public Health Threat, Micorbial Bioactives, 6(1), 1-10, 910A
Johnson, E., & White, B. (2017). Organic Synthesis: Principles and Applications. Oxford University Press.
Jones, K., et al. (2020). The Role of Heterocyclic Compounds in Medicinal Chemistry: A Review. Journal of Medicinal Chemistry, 63(15), 8725-8761.
Kaushik, C. P., Luxmi, R., Kumar, M., Singh, D., Kumar, K., & Pahwa, A. (2019). One-pot facile synthesis, crystal structure and antifungal activity of 1, 2, 3-triazoles bridged with amine-amide functionalities. Synthetic Communications, 49(1), 118-128.
Lee, H., & Kim, Y. (2018).
Llor, C., & Bjerrum, L. (2014). Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Therapeutic advances in drug safety, 5(6), 229-241.
Malik, B., & Bhattacharyya, S. (2019). Antibiotic drug-resistance as a complex system driven by socio-economic growth and antibiotic misuse. Scientific reports, 9(1), 9788.
Miller, G., & Wilson, J. (2020). NMR Spectroscopy: Principles and Applications. John Wiley & Sons.Roberts, M., & Cooper, R. (2019). Antibacterial Mechanisms of Action: A Review. Journal of Antibiotics, 72(3), 304-325.
Muntaha R. Ibraheem, Dhafar N. Al-Ugaili. (2024). Nanoparticle-Mediated Plasmid Curing in Combating Antibiotic Resistance in Pathogenic Bacteria, Journal of Angiotherapy, 8(3), 1-8, 9495
Musharrat Jahan Prima, Masriana Hassan, Juhi Sharma. (2023), Novel Approaches for Combating Antibiotic Resistance in Pathogenic Bacteria, Microbial Bioactives, 6(1), 1-18, 9373
Naaz, F., Pallavi, M. P., Shafi, S., Mulakayala, N., Yar, M. S., & Kumar, H. S. (2018). 1, 2, 3-triazole tethered Indole-3-glyoxamide derivatives as multiple inhibitors of 5-LOX, COX-2 & tubulin: Their anti-proliferative & anti-inflammatory activity. Bioorganic chemistry, 81, 1-20.
Phatak, P. S., Bakale, R. D., Dhumal, S. T., Dahiwade, L. K., Choudhari, P. B., Siva Krishna, V., … & Haval, K. P. (2019). Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1, 2, 3-triazoles. Synthetic communications, 49(16), 2017-2028.
Rostovtsev, V. V., Green, L. G., Fokin, V. V., & Sharpless, K. B. (2002). A stepwise huisgen cycloaddition process: copper (I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angewandte Chemie International Edition, 41(14), 2596-2599.
Saeedi, M., Mohammadi-Khanaposhtani, M., Pourrabia, P., Razzaghi, N., Ghadimi, R., Imanparast, S., ... & Akbarzadeh, T. (2019). Design and synthesis of novel quinazolinone-1, 2, 3-triazole hybrids as new anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and docking study. Bioorganic chemistry, 83, 161-169.
Sahoo, J., Kshiroda, P. R. I. Y. A. M. B. A. D. A., Sarangi, N., Rout, S., & Paidesetty, S. (2020). In silico investigation and biological evaluation of synthesized sulfamethoxazole derivatives. Indian J Pharm Sci, 82(1), 123-130.
Sanjana Mahbub Supty, Tarif Md Faiyaz Saadat, Khondoker Tanjim Islam. (2023). Multidrug Resistance and Molecular Characterization of Klebsiella spp. Isolated from the Cloacal Samples of Broiler Chickens in Bangladesh, Microbial Bioactives, 6(1), 1-11, 9419
Sathya, A., Ramalingam, S., Nagabalasubramaniyan, P. B., & Karpagam, J. (2021). Structure activity investigation, CT complex analysis and spectroscopic investigation on antibiotic drug; Sulfamethoxazole using quantum chemical calculations. Chemical Physics Impact, 3, 100031.
Settypalli, T., Chunduri, V. R., Maddineni, A. K., Begari, N., Allagadda, R., Kotha, P., & Chippada, A. R. (2019). Design, synthesis, in silico docking studies and biological evaluation of novel quinoxaline-hydrazide hydrazone-1, 2, 3-triazole hybrids as α-glucosidase inhibitors and antioxidants. New Journal of Chemistry, 43(38), 15435-15452.
Shaima H. Abdullah, Mahmoud M. Salih, Khalid, A. Al-Badrany. (2024). Synthesis, characterization and Antibacterial Evaluation of Novel Thiazolidine Derivatives, Journal of Angiotherapy, 8(3), 1-6, 9501
Singh, K., Gangrade, A., Jana, A., Mandal, B. B., & Das, N. (2019). Design, synthesis, characterization, and antiproliferative activity of organoplatinum compounds bearing a 1, 2, 3-triazole ring. ACS Omega, 4(1), 835-841.
Smith, P., & Jones, L. (2022). Advances in Antibacterial Drug Discovery: A Comprehensive Overview. Antibiotics, 11(4), 267.
Smith, T., et al. (2018). Structural Modification of Antibiotics: Recent Developments. European Journal of Medicinal Chemistry, 157, 1175-1189.
Tornøe, C. W., Christensen, C., & Meldal, M. (2002). Peptidotriazoles on solid phase:[1, 2, 3]-triazoles by regiospecific copper (I)-catalyzed 1, 3-dipolar cycloadditions of terminal alkynes to azides. The Journal of organic chemistry, 67(9), 3057-3064.
Wilson, R., et al. (2019). Molecular Docking Studies in Drug Discovery: A Review. Frontiers in Chemistry, 7, 559
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