Medicinal Chemistry Research

, Volume 27, Issue 2, pp 458–469 | Cite as

Convenient synthesis, antimalarial and antimicrobial potential of thioethereal 1,4-disubstituted 1,2,3-triazoles with ester functionality

  • C. P. Kaushik
  • Ashima Pahwa
Original Research


This paper elicits the synthesis of twenty five 1,4-disubstituted 1,2,3-triazole analogs (5a5y) comprising thioether and ester linkages from aryl(prop-2-yn-1-yl)sulfanes and benzyl 2-azidoacetates employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition. Structures of synthesized compounds were elucidated by spectroscopic techniques like FTIR, 1H NMR, 13C NMR, and HRMS. Newly synthesized compounds were screened for in vitro antimalarial evaluation against P. falciparum strain and microbicidal potential against B. subtilis, S. epidermidis, E. coli, P. aeruginosa, C. albicans, and A. niger. Some of synthesized triazoles displayed moderate antimalarial activity against tested strain, while, the compounds 5i and 5n were found to exhibit significant inhibitory activity against most of the tested microbial strains.


Antimalarial evaluation Antimicrobial potential Click chemistry 1,4-Disubstituted 1,2,3-triazoles Huisgen 1,3-dipolar cycloaddition 



The authors are highly thankful to University Grants Commission, New Delhi for financial assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2072_MOESM1_ESM.docx (4.8 mb)
Supplementary Information


  1. Balabadra S, Kotni MK, Manga V, Allanki AD, Prasad R, Sijwali PS (2017) Synthesis and evaluation of naphthyl bearing 1,2,3-triazole analogs as antiplasmodial agents, cytotoxicity and docking studies. Bioorg Med Chem 25:221–232CrossRefPubMedGoogle Scholar
  2. Banday AH, Shameem AS, Ganai BA (2012) Antimicrobial studies of unsymmetrical bis-1,2,3-triazoles. Org Med Chem Lett 2:2191–2858CrossRefGoogle Scholar
  3. Buckle DR, Rockell CJM, Smith H, Spicer BA (1986) Studies on 1,2,3-triazoles(piperazinylalkoxy)-[1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties. J Med Chem 29:2262–2267CrossRefPubMedGoogle Scholar
  4. Desjardins RE (1984) In vitro techniques for antimalarial development and evaluation. In: Peters W, Richards WHG eds Handbook of experimental pharmacology. Springer, Heidelberg, p 179–200Google Scholar
  5. D’hooghe M, Vandekerckhove S, Mollet K, Vervisch K, Dekeukeleire S, Lehoucq L, Latedgan C, Smith PJ, Chibale K, Kimpe ND (2011) Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity. Beilstein J Org Chem 7:1745–1752CrossRefPubMedPubMedCentralGoogle Scholar
  6. Dubey N, Sharma MC, Kumar A, Sharma P (2015) A click chemistry strategy to synthesize geraniol-coupled 1,4-disubstituted 1,2,3-triazoles and exploration of their microbicidal and antioxidant potential with molecular docking profile. Med Chem Res 24:2717–2731CrossRefGoogle Scholar
  7. Dügdü E, Ünlüer D, Çelik F, Sancak K, Karaoglu SA, Özel A (2016) Synthesis of novel symmetrical 1,4-disubstituted 1,2,3-bistriazole derivatives via ‘click chemistry’ and their biological evaluation. Molecules 21:659–672CrossRefGoogle Scholar
  8. Ferreira SB, Sodero ACR, Cardoso MFC, Lima ES, Kaiser CR, Silva Jr. FP, Ferreira VF (2010) Synthesis, biological activity, and molecular modeling studies of 1H-1,2,3-triazole derivatives of carbohydrates as r-glucosidases inhibitors. J Med Chem 53:2364–2375CrossRefPubMedGoogle Scholar
  9. Friscourt F, Boons GJ (2010) One-pot three-step synthesis of 1,2,3-triazoles by copper-catalyzed cycloaddition of azides with alkynes formed by a sonogashira cross-coupling and desilylation. Org Lett 12:4936–4939CrossRefPubMedPubMedCentralGoogle Scholar
  10. Gilla C, Jadhava G, Shaikha M, Kalea R, Ghawalkara A, Nagargoje D, Shiradkar M (2008) Clubbed [1,2,3] triazoles by fluorine benzimidazole: a novel approach to H37Rv inhibitors as a potential treatment for tuberculosis. Bioorg Med Chem Lett 18:6244–6247CrossRefGoogle Scholar
  11. Głowacka IE, Balzarini J, Wróblewski AE (2012) Design, synthesis, antiviral, and cytotoxic evaluation of novel phosphonylated 1,2,3-triazoles as acyclic nucleotide analogs. Nucleosides Nucleotides Nucleic Acids 31:293–318CrossRefPubMedGoogle Scholar
  12. He R, Chen Y, Chen Y, Ougolkov AV, Zhang JS, Savoy DN, Billadeau DD, Kozikowski AP (2010) Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents. J Med Chem 53:1347–1356CrossRefPubMedPubMedCentralGoogle Scholar
  13. Horne WS, Yadav MK, Stout CD, Ghadiri MR (2004) Heterocyclic peptide backbone modifications in an α-helical coiled coil. J Am Chem Soc 126:15366–15367CrossRefPubMedPubMedCentralGoogle Scholar
  14. Huisgen R, Szeimies G, Moebius L (1967) 1.3-Dipolare Cycloadditionen, XXXII. Kinetik der Additionen organischer Azide an CC-Mehrfachbindungen. Chem Ber 100:2494–2507Google Scholar
  15. Jørgensen AS, Shaikh KI, Enderlin G, Ivarsen E, Kumar S, Nielsen P (2011) The synthesis of double-headed nucleosides by the CuAAC reaction and their effect in secondary nucleic acid structures. Org Biomol Chem 9:1381–1388CrossRefPubMedGoogle Scholar
  16. Karakurt A, Ayetmir MD, Stables JP, Ozalp M, Kaynak FB, Ozbey S, Dalkara S (2006) Synthesis of some oxime ether derivatives of 1-(2-naphthyl)-2-(1,2,4-triazol-1-yl)ethanone and their anticonvulsant and antimicrobial activities. Arch Pharm Chem Life Sci 339:513–520CrossRefGoogle Scholar
  17. Kaushik CP, Kumar K, Lal K, Singh SK (2014a) Synthesis, characterization and microbicidal activity of some (1-substituted-1H-1,2,3-triazol-4-yl)methyl benzoates. Chem Biol Interface 4:341–350Google Scholar
  18. Kaushik CP, Kumar K, Narasimhan B, Singh D, Kumar P, Pahwa A (2016b) Synthesis, antimicrobial activity and QSAR studies of amide-ester linked 1,4-disubstituted 1,2,3-triazoles. Monatsh Chem
  19. Kaushik CP, Kumar K, Lal K, Narasimhan B, Kumar A (2016c) Synthesis and antimicrobial evaluation of 1,4-disubstituted 1,2,3-triazoles containing benzofused N-heteroaromatic moieties. Monatsh Chem 147:817–828CrossRefGoogle Scholar
  20. Kaushik CP, Kumar K, Singh D, Singh SK, Jindal DK, Luxmi R (2015) Synthesis, characterization, and antimicrobial potential of some 1,4-disubstituted 1,2,3-bistriazoles. Synth Commun 45:1977–1985CrossRefGoogle Scholar
  21. Kaushik CP, Kumar K, Singh SK, Singh D, Saini S (2016a) Synthesis and antimicrobial evaluation of 1,4-disubstituted 1,2,3-triazoles with aromatic ester functionality. Arab J Chem 9:865–871CrossRefGoogle Scholar
  22. Kaushik CP, Lal K, Kumar A, Kumar S (2014b) Synthesis and biological evaluation of amino acid-linked 1,2,3-bistriazole conjugates as potential antimicrobial agents. Med Chem Res 23:2995–3004CrossRefGoogle Scholar
  23. Kaushik CP, Pahwa A, Thakur R, Kaur P (2017) Regioselective synthesis and antimicrobial evaluation of some thioether–amide linked 1,4-disubstituted 1,2,3-triazoles. Synth Commun 47:368–378CrossRefGoogle Scholar
  24. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021CrossRefGoogle Scholar
  25. Kumar K, Biot C, Kremer SC, Kremer L, Guérardel Y, Roussel P, Kumar V (2013) Base-promoted expedient access to spiroisatins: synthesis and antitubercular evaluation of 1h‑1,2,3-triazole-tethered spiroisatin−ferrocene and isatin−ferrocene conjugates. Organometallics 32:7386–7398CrossRefGoogle Scholar
  26. Kumbhare RM, Dadmal TL, Pamanji R, Kosurkar UB, Velatooru LR, Appalanaidu K, Rao YK, Rao JV (2014) Synthesis of novel fluoro 1,2,3-triazole tagged amino bis(benzothiazole) derivatives, their antimicrobial and anticancer activity. Med Chem Res 23:4404–4413CrossRefGoogle Scholar
  27. Lal K, Kumar A, Pavan MS, Kaushik CP (2012) Regioselective synthesis and antimicrobial studies of ester linked 1,4-disubstituted 1,2,3-bistriazoles. Bioorg Med Chem Lett 22:4353–4357CrossRefPubMedGoogle Scholar
  28. Lambros C, Vanderberg JP (1979) Synchronization of Plasmodium falciparum intraerythrocytic stages in culture. J Parasitol 65:418–420CrossRefPubMedGoogle Scholar
  29. Nagesh HN, Suresh N, Prakash GVSB, Gupta S, Rao JV, Sekhar KVGC (2015) Synthesis and biological evaluation of novel phenanthridinyl piperazine triazoles via click chemistry as anti-proliferative agents. Med Chem Res 24:523–532CrossRefGoogle Scholar
  30. Panjarathinam R (2007) Text book of medicalparasitology, 2nd Edition. Orient Longman Pvt. Ltd., Chennai, p 329–331Google Scholar
  31. Rieckmann KH, Campbell GH, Sax LJ, Mrema JE (1978) Drug sensitivity of Plasmodium falciperum, an in vitro microtechnique. Lancet 1:221–223Google Scholar
  32. Singh J (1956) J.S.B. stain: a review. Indian J Malariol 10:117–129PubMedGoogle Scholar
  33. Singh P, Raj R, Kumar V, Mahajan MP, Bedi PM, Kaur T, Saxena AK (2012) 1,2,3-Triazole tethered b-lactam-chalcone bifunctional hybrids: synthesis and anticancer evaluation. Eur J Med Chem 47:594–600CrossRefPubMedGoogle Scholar
  34. Tornфe 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 67:3057–3064CrossRefGoogle Scholar
  35. Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. Science 193:673–675CrossRefPubMedGoogle Scholar
  36. Vasilevsky SF, Baranov DS, Govdi AI, Sorokina IV, Tolstikova TG, Tolstikov GA, Alabugin IV (2014) Click chemistry on diterpenes: anti-inflammatory activity of the acetylenic derivatives of levopimaric acid and products of their transformations. ARKIVOC (v):145–157Google Scholar
  37. Whiting M, Tripp JC, Lin YC, Lindstrom W, Olson AJ, Elder JH, Sharpless KB, Fokin VV (2006) Rapid discovery and structure–activity profiling of novel inhibitors of human immunodeficiency virus type 1 protease enabled by the copper(i)-catalyzed synthesis of 1,2,3-triazoles and their further functionalization. J Med Chem 49:7697–7710CrossRefPubMedGoogle Scholar
  38. Zhang HZ, Wei HZ, Kumar KV, Rasheed S, Zhou CH (2015) Synthesis and biological evaluation of novel d-glucose-derived 1,2,3-triazoles as potential antibacterial and antifungal agents. Med Chem Res 24:182–196CrossRefGoogle Scholar
  39. Zhou L, Amer A, Korn M, Burda R, Balzarini J, Clercq ED, Kern ER, Torrence PF (2005) Synthesis and antiviral activities of 1,2,3-triazole functionalized thymidines: 1,3-dipolar cycloaddition for efficient regioselective diversity generation. Antivir Chem Chemother 16:375–383CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of ChemistryGuru Jambheshwar University of Science & TechnologyHisarIndia

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