Synthesis and bioevaluation of α,α’-bis(1H-1,2,3-triazol-5-ylmethylene) ketones

  • Tejshri R. Deshmukh
  • Vagolu S. Krishna
  • Dharmarajan Sriram
  • Jaiprakash N. Sangshetti
  • Bapurao B. ShingateEmail author
Original Paper


Curcumin is an active component of turmeric that has poor solubility, stability and bioavailability. The monocarbonyl curcumin analogues were modified from curcumin to achieve more stable and active compounds as compared to curcumin. Therefore, we have designed and synthesized a library of 18 compounds of α,α’-bis(1H-1,2,3-triazol-5-ylmethylene) ketones (8ao) and evaluated them for their in vitro antitubercular and antioxidant activities against their respective strains. Results of biological activities reveal that some of the compounds from the series showed good antitubercular as well as antioxidant activities. The compound 8l was found as the most active antitubercular agent with MIC value 3.125 µg/mL, against Mtb H37Rv. Moreover, the compounds, 8c, 8d, 8e and 8g, also showed potent antitubercular activity. The compounds 8e and 8m displayed potent antioxidant activities with IC50 values 15.60 and 15.49 µg/mL, respectively. In support of the bioactivities, in silico ADME properties’ prediction has also been carried out in this study.

Graphic Abstract


α,α’-bis(1H-1,2,3-triazol-5-ylmethylene) ketones Curcumin Antitubercular activity Antioxidant activity 



The authors are thankful to the Head, Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-431 004, India for providing laboratory facility.


  1. Agalave SG, Maujan SR, Pore VS (2011) Click chemistry: 1,2,3-triazoles as pharmacophores. Chem Asian J 6:2696–2718. CrossRefPubMedGoogle Scholar
  2. Ali AA, Gogoi D, Chaliha AK, Buragohain AK, Trivedi P, Saikia PJ, Gehlot PS, Kumar A, Chaturvedi V, Sarma D (2017) Synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents. Bioorg Med Chem Lett 27:3698–3703. CrossRefGoogle Scholar
  3. Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7. CrossRefPubMedGoogle Scholar
  4. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818. CrossRefPubMedGoogle Scholar
  5. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB (2008) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol 76:1590–1611. CrossRefPubMedGoogle Scholar
  6. Archie SR, Das BK, Hossain MDS, Kumar U, Rouf ASS (2017) Synthesis and antioxidant activity of 2-substituted-5-nitro benzimidazole derivatives. Int J Pharm Pharm Sci 9:308–310. CrossRefGoogle Scholar
  7. Banday AH, Shameem SA, Ganai BA (2012) Antimicrobial studies of unsymmetrical bis-1,2,3-triazoles. Org Med Chem Lett 13:2–7. CrossRefGoogle Scholar
  8. Boechat N, Ferreira VF, Ferreira SB, Ferreira ML, da Silva FC, Bastos MM, Costa MS, Lourenco MC, Pinto AC, Krettli AU, Aguiar AC, Teixeira BM, da Silva NV, Martins PR, Bezerra FA, Camilo AL, da Silva GP, Costa CC (2011) Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain. J Med Chem 54:5988–5999. CrossRefPubMedGoogle Scholar
  9. Costa MS, Boechat N, Rangel EA, Silva FC, de Souza AMT, Rodrigues CR, Castro HC, Junior IN, Lourenco MCS, Wardell SMSV, Ferreira VF (2006) Synthesis, tuberculosis inhibitory activity, and SAR study of N-substituted-phenyl-1,2,3-triazole derivatives. Bioorg Med Chem 14:8644–8653. CrossRefPubMedGoogle Scholar
  10. Danne AB, Choudhari AS, Chakraborty S, Sarkar D, Khedkar VM, Shingate BB (2018) Triazole-diindolylmethane conjugates as new antitubercular agents: synthesis, bioevaluation, and molecular docking. MedChemComm 9:1114–1130. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Dheer D, Singh V, Shankar R (2017) Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorg Chem 71:30–54. (references cited theirin) CrossRefPubMedGoogle Scholar
  12. Drug-likeness and molecular property prediction. Accessed 11 Dec 2018
  13. Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G, Hernandez A, Degnan MT, Cook MB, Quenzer VK, Ferguson RM, Gilman RH (1998) Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J Clin Microbiol 36:362–366. PubMedPubMedCentralGoogle Scholar
  14. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65:1631–1652. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Jordao AK, Afonso PP, Ferreira VF, de Souza MC, Almeida MC, Beltrame CO, Paiva DP, Wardell SM, Wardell JL, Tiekink ERT, Damaso CR, Cunha AC (2009) Antiviral evaluation of N-amino-1,2,3-triazoles against Cantagalo virus replication in cell culture. Eur J Med Chem 44:3777–3783. CrossRefPubMedGoogle Scholar
  16. Khare SP, Deshmukh TR, Sangshetti JN, Krishna VS, Sriram D, Khedkar VM, Shingate BB (2018) Design, synthesis and molecular docking studies of novel triazole-chromene conjugates as antitubercular, antioxidant and antifungal agents. ChemistrySelect 3:13113–13122. CrossRefGoogle Scholar
  17. Kinsella JE, Frankel E, German B, Kanner J (1993) Possible mechanisms for the protective role of antioxidants in wine and plant foods. Food Technol 47:85–89Google Scholar
  18. Kolb HC, Sharpless KB (2003) The growing impact of click chemistry on drug discovery. Drug Discovery Today 8:1128–1137. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021.;2-5 CrossRefGoogle Scholar
  20. Lahsasni SA, Korbi FHA, Aljaber NAA (2014) Synthesis, characterization and evaluation of antioxidant activities of some novel chalcones analogues. Chem Cent J 8:32–41. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Lima-Neto RG, Cavalcante NNM, Srivastava RM, Mendonca FJB, Wanderley AG, Neves, dos Anjos JV (2012) Synthesis of 1,2,3-triazole derivatives and in vitro antifungal evaluation on Candida strains. Molecules 17:5882–5892. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Lipinski CA, Lombardo L, Dominy BW, Feeney P (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. J Adv Drug Deliv Rev 46:3–26CrossRefGoogle Scholar
  23. Liu Z, Sun Y, Ren L, Huang Y, Cai Y, Weng Q, Shen X, Li X, Liang G, Wang Y (2013) Evaluation of a curcumin analog as an anti-canceragent inducing ER stress-mediated apoptosis innon-small cell lung cancer cells. BMC Cancer 13:494. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Mady MF, Awad GEA, Jorgensen KB (2014) Ultasound-assisted synthesis of novel 1,2,3-triazoles coupled diaryl sulfone moieties by the CuAAC reaction, and biological evaluation of them as antioxidant and antimicrobial agents. Eur J Med Chem 84:433–443. CrossRefPubMedGoogle Scholar
  25. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087. CrossRefPubMedGoogle Scholar
  26. Mandalapu D, Saini KS, Gupta S, Sharma V, Malik MY, Chaturvedi S, Bala V, Hamidullah Thakur S, Maikhuri JP, Wahajuddin M, Konwar R, Gupta G, Sharma VL (2016) Synthesis and biological evaluation of some novel triazole hybrids of curcumin mimics and their selective anticancer activity against breast and prostate cancer cell lines. Bioorg Med Chem Lett 26:4223–4232. CrossRefPubMedGoogle Scholar
  27. Manohar S, Khan SI, Kandi SK, Raj K, Sun G, Yang X, Molina ADC, Ni N, Wang B, Rawat DS (2013) Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin. Bioorg Med Chem Lett 23:112–116. CrossRefPubMedGoogle Scholar
  28. Molinspiration Chemoinformatics Brastislava, Slovak Republic (2014) Accessed 10 Dec 2018
  29. Mosley CA, Liotta DC, Snyder JP (2007) Highly active anticancer curcumin analogues. Adv Exp Med Biol 595:77–103. CrossRefPubMedGoogle Scholar
  30. Nucci M, Marr KA (2005) Emerging fungal diseases. Clin Infect Dis 41:521–526. CrossRefPubMedGoogle Scholar
  31. Pokhodylo N, Shyyka O, Matiychuk V (2013) Synthesis of 1,2,3-Triazole derivatives and evaluation of their anticancer activity. Sci Pharm 81:663–676. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Raj R, Singh P, Singh P, Gut J, Rosenthal PJ, Kumar V (2013) Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: synthesis and antimalarial evaluation. Eur J Med Chem 62:590–596. CrossRefPubMedGoogle Scholar
  33. Samaan N, Zhong Q, Fernandez J, Chen G, Hussain AM, Zheng S, Wang G, Chen QH (2014) Design, Synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents. Eur J Med Chem 75:123–131. CrossRefPubMedPubMedCentralGoogle Scholar
  34. Temel E, Alasalvar C, Gokce H, Guder A, Albayrak C, Alpaslan YB, Alpaslan G, Dilek N (2014) DFT calculations, spectroscopy and antioxidant activity studies on (E)-2-nitro-4-[(phenylimino)methyl]phenol. Spectrochim Acta A Mol Biomol Spectrosc 136B:534–546. CrossRefGoogle Scholar
  35. Tornoe CW, 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. J Org Chem 67:3057–3064.CrossRefPubMedGoogle Scholar
  36. Wang Y, Xiao J, Zhou H, Yang S, Wu X, Jiang C, Zhao Y, Liang D, Li X, Liang G (2011) A novel monocarbonyl analogue of curcumin, (1E,4E)-1,5-bis (2,3-dimethoxyphenyl)penta-1,4-dien-3-one, induced cancer cell H460 apoptosis via activation of endoplasmic reticulum stress signaling pathway. J Med Chem 54:3768–3778.CrossRefPubMedGoogle Scholar
  37. Wang R, Chen C, Zhang X, Zhang C, Zhong Q, Chen G, Zhang Q, Zheng S, Wang G, Chen QH (2015) Structure-activity relationship and pharmacokinetic studies of 1,5-Diheteroarylpenta-1,4-dien-3-ones: a class of promissing curcumin-based anticancer agents. J Med Chem 58:4713–4726. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Zhao YH, Abraham MH, Le (2002) Rate-limited steps of human oral absorption and QSAR studies. J Pharm Res 19:1446–1457CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2019

Authors and Affiliations

  • Tejshri R. Deshmukh
    • 1
  • Vagolu S. Krishna
    • 2
  • Dharmarajan Sriram
    • 2
  • Jaiprakash N. Sangshetti
    • 3
  • Bapurao B. Shingate
    • 1
    Email author
  1. 1.Department of ChemistryDr. Babasaheb Ambedkar Marathwada UniversityAurangabadIndia
  2. 2.Department of PharmacyBirla Institute of Technology and Science-PilaniHyderabadIndia
  3. 3.Department of Pharmaceutical ChemistryY. B. Chavan College of PharmacyAurangabadIndia

Personalised recommendations