SYNTHESIS AND EVALUATION OF DIAZO-TRIAZOLE HYBRID AS ANTI-TUBERCULAR AGENTS
DOI:
https://doi.org/10.22159/ijcr.2025v9i4.281Keywords:
Anti-tubercular, Diazenyl, Triazole, Diazotization, ClickAbstract
Objective: To find novel anti-tubercular agents by using diazo-triazole hybrid. A series of new(E)-4-((2,4-dichloro-3-((substituted)diazenyl)phenoxy)methyl)-1-(substituted)-1H’-1,2,3-triazole derivatives (6a-6m) were synthesized from readily available anilines (1a-1d) and 2, 4-dichlorophenol (2). A total of 21 novel diazenyl-triazole derivatives were synthesized. Diazotization and click reactions were used in a sequence of processes to create the targets.
Methods: Merck and Sigma-Aldrich provided analytical grade (AR) chemicals and reagents, which were employed directly without further purification. All FT-IR spectra were recorded using a Bruker Alpha FT-IR spectrophotometer (Billerica, MA, USA) with the universal ATR sampling attachment. The 1H, 13C, and 19F NMR spectra of all synthesized compounds were recorded.
Results: The synthesized derivatives are characterized by FT-IR, 1H NMR, 19F, and 13C NMR analytical techniques. The anti-tubercular (Mycobacterium tuberculosis: H37Rv strain) properties of the novel compounds were evaluated in vitro. Many compounds exhibited moderate to good activity. The compounds 3a, 3b, 3d and 6i showed good inhibition (MIC = 6.25-12.5 µm) against H37Rv strain.
Conclusion: The synthesized compounds exhibited good antimicrobial activity and can serve as potent agent against antimicrobial agents. Other derivatives showed moderate to lower inhibition for all the strains.
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References
Morens DM, Folkers GK, Fauci AS. The challenge of emerging and re-emerging infectious diseases. Nature. 2004 Jul 8;430(6996):242–9.
World Health Organization. Global Tuberculosis Report 2015 [Internet]. Geneva: WHO; 2015 [cited 2025 May 15]. Available from: http://www.who.int/tb/country/en/
World Health Organization. Global Tuberculosis Report 2018 [Internet]. Geneva: WHO; 2018 [cited 2025 May 15]. Available from: https://www.who.int/tb/publication/global_report/en/
Jakab Z, Acosta CD, Kluge HH, Dara M. Consolidated action plan to prevent and combat multidrug and extensively drug-resistant tuberculosis in the WHO European region 2011–2015: cost-effectiveness analysis. Tuberculosis (Edinb). 2015;95 Suppl 1:S212–6.
Mikusova K, Ekins S. Learning from past for TB drug discovery in the future. Drug Discov Today. 2017 Apr;22(3):534–45.
Cole ST. Tuberculosis drug discovery needs public–private consortia. Drug Discov Today. 2016 Mar;22(3):477–8.
Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020 Mar 5;382(10):893–902.
Thwaites G, Nahid P. Triumph and tragedy of 21st century tuberculosis drug development. N Engl J Med. 2020 Mar 5;382(10):959–60.
Makarov V, Salina E, Reynolds RC, Zin PPK, Ekins S. Molecule property analyses of active compounds for Mycobacterium tuberculosis. J Med Chem. 2020; doi:10.1021/acs.jmedchem.9b02075
Iacobino A, Piccaro G, Giannoni F, Mustazzolu A, Fattorini L. Fighting tuberculosis by drug targeting non replicating Mycobacterium tuberculosis bacilli. Int J Mycobacteriol. 2017 Sep;6(3):213–21.
Zhang S, Xu Z, Gao C, Ren Q-C, Chang L, Lv Z-S, et al. Triazole derivatives and their anti-tubercular activity. Eur J Med Chem. 2017 Jul 20;138:501–13.
Thirumurgan P, Matosiuk D, Jozwiak K. Click chemistry for drug development and diverse chemical-biological applications. Chem Rev. 2013 Sep 11;113(7):4905–79.
Xu Z, Song X-F, Hu Y-Q, Qiang M, Lv Z-S. Azide-alkyne cycloaddition towards 1H-1,2,3-triazole-tethered gatifloxacin and isatin conjugate: design, synthesis and in vitro anti-mycobacterial evaluation. Eur J Med Chem. 2017 Jul 20;138:66–71.
Thomas KD, Adhikari AV, Chowdhury IH, Sumesh E, Pal NK. New quinolin-4-yl-1,2,3-triazoles carrying amides, sulphonamides and amidopiperazines as potent anti-tubercular agents. Eur J Med Chem. 2011 Jul;46(7):2503–12.
Zhou CH, Wang Y. Recent researches in triazole compounds as medicinal drugs. Curr Med Chem. 2012;19(2):239–80.
Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed Engl. 2002;41(14):2596–9.
Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl. 2001;40(11):2004–21.
Boechat N, Ferreira VF, Ferreira SB, Ferreira MLG, Da Silva FC, Bastos MM, et al. Synthesis and antimalarial activity of new 1,2,3-triazole derivatives. J Med Chem. 2011 Sep 8;54(17):5988–98.
Dheer D, Singh V, Shankar R. Medicinal attributes of 1,2,3-triazoles: current developments. Bioorg Chem. 2017 Apr;71:30–54.
Awad IM, Aly AA, Abdel RA, Ahmed SH. Synthesis and characterization of some new transition metal complexes. J InorgBiochem. 1998;33:77–89.
Phillips OA, Udo EE, Abdel-Hamid ME, Varghese R. Synthesis and antimicrobial activity of some triazole derivatives. Eur J Med Chem. 2009 Sep;44(9):3217–27.
Funar-Timofei S, Fabian WMF, Kurunczi L, Goodarzi M. Quantitative structure–activity relationship modeling of dyes. Dyes Pigm. 2012 Jul;94(2):278–89.
Singh H, Sindhu J, Khurana JM, Sharma C, Aneja KR. Synthesis, biological evaluation and photophysical studies of novel 1,2,3-triazole linked azo dyes. RSC Adv. 2014;4:5915–25.
Selvarani S, Rajakumar P. Synthesis, photochemical, electrochemical and cytotoxic studies on azobenzene cored dendrimer decorated with chalcone motif. ChemSel. 2018 Oct;3(18):5455–60.
Kidwai S, Park CY, Mawatwal S, Tiwari P, Jung MG, Gosain TP, et al. Dual mechanism of action of 5-nitro-1,10-phenanthroline against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2017 Aug;61(8):e00015-17.
Elzupir, A. O., A. E. M. Saeed, I. E. BARAKAT, and J. H. V. D. Westhuizen. “ULTRASOUND-ASSISTED MICROWAVE SYNTHESIS AND MECHANISTIC ASPECT OF 2-AMINO-4, 6-DIARYL PYRIMIDINES AND 3, 5-DIARYL-1H- PYRAZOLES”. International Journal of Current Pharmaceutical Research, vol. 7, no. 1, Jan. 2015, pp. 7-12.
Jalihal, P. C., V. Rajoriya, and V. Kashaw. “DESIGN, SYNTHESIS, AND EVALUATION OF NEW DERIVATIVE OF 1,2,4-TRIAZOLES FOR ANTIMICROBIAL AND ANTI-INFLAMMATORY ACTIVITY”. International Journal of Current Pharmaceutical Research, vol. 10, no. 4, July 2018, pp. 29-35, doi:10.22159/ijcpr.2018v10i4.28455.
THOMAS, A., V. B., S. S. K. U., and V. M. V. “DEVELOPMENT OF NOVEL 1, 3, 4-THIADIAZOLES AS ANTITUBERCULAR AGENTS-SYNTHESIS AND IN VITRO SCREENING”. International Journal of Current Pharmaceutical Research, vol. 15, no. 3, May 2023, pp. 37-41, doi:10.22159/ijcpr.2023v15i3.3009.
Verma, S. K., Verma, R., Verma, S., Vaishnav, Y., Tiwari, S. P., & Rakesh, K. P. (2020). Anti-tuberculosis activity and its structure-activity relationship (SAR) studies of oxadiazole derivatives: A key review. European Journal of Medicinal Chemistry, 112886. doi: 10.1016/j.ejmech.2020.112886.
Bakale RD, Sulakhe SM, Kasare SL, Sathe BP, Rathod SS, Choudhari PB, Madhu Rekha E, Sriram D, Haval KP. Design, synthesis and antitubercular assessment of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives. Bioorg Med Chem Lett. 2024 Jan 1;97:129551. doi: 10.1016/j.bmcl.2023.129551. Epub 2023 Nov 17. PMID: 37979730.
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Copyright (c) 2025 DINESH KACHKURE, SACHIN A. DHAWALE, GANESH TAPADIYA, CHANDRAKANT PAWAR, JAGDISH BHARAD
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