Triazole-based click chemistry as strategic for novel therapeutics treatments of cancer: A bibliometric analysis 2007–2024

Wilson Cardona-Galeano Andres F. Yepes Howard Ramírez-Malule   

Open Access   

Published:  Feb 27, 2025

DOI: 10.7324/JAPS.2025.221899
Abstract

Click chemistry is nowadays a versatile strategy for obtaining new bioactive compounds for different diseases, including cancer. Click strategy-based synthetic approaches offer effective routes for the rapid and mild production of bioactive compounds. Triazole ring is known to have significant pharmaceutical value because its derivatives have been shown to have a variety of pharmacological actions, including cancer. There are numerous techniques for triazole ring construction, but click chemistry offers a quick, selective, and dependable approach. The reaction of an azide with a terminal alkyne based on the CuI-catalyzed Huisgen 1,3-dipolar cycloaddition to create 1,2,3-triazoles is the most frequent reaction in click chemistry. The resulting triazole ring is essential in the composition of some clinically approved drugs and other compounds with strong anticancer effects since this fragment may help to improve selectivity, optimize pharmacokinetic features, and overcome resistance. This work shows a bibliometric analysis of published studies on click chemistry and their application in the synthesis of hybrid and conjugate molecules with anticancer activity. Also, we revealed that molecular docking showed the possible mechanism of action of some compounds. Furthermore, bibliometric analysis is shown, providing a holistic overview of the areas in which click chemistry investigations have been focused. Chemistry, materials science, chemical engineering, pharmacology, toxicology and pharmaceutics, and biochemistry, genetics, and molecular biology were the primary fields of study in the field. Finally, the findings show that there has been a notable increase in study on click chemistry, its hybrids, and conjugates, with molecular docking simulations emerging as a new field.


Keyword:     Click chemistry triazole hybrids anticancer activity bibliometric analysis


Citation:

Cardona-Galeano W, Yepes AF, Ramírez-Malule H. Triazole-based click chemistry as strategic for novel therapeutics treatments of cancer: A bibliometric analysis 2007–2024. J Appl Pharm Sci. 2025. Online First. http://doi.org/10.7324/JAPS.2025.221899

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan 12;71(1):7-33. https://doi.org/10.3322/caac.21654

2. WHO. Cancer today. Geneva, Switzerland: WHO; 2022. Available from: https://gco.iarc.fr/en?Mode=cancer&groupp+o+p+u+l+a+t+ions=1&+;+s+exes=0&+;+p+o+p+u+l+a+t+ions=90+0&types=0_1&sort_by=value1

3. NIH. What is cancer? 2021. Available from: https://Www.Cancer.Gov/about-Cancer/Understanding/What-Is-Cancer

4. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019 Sep 11;69(5):363-85. https://doi.org/10.3322/caac.21565

5. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull. 2017 Sep 25;7(3):339-48. https://doi.org/10.15171/apb.2017.041

6. Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, et al. New approaches and procedures for cancer treatment: current perspectives. SAGE Open Med. 2021 Jan 12;9:20503121211034366. https://doi.org/10.1177/20503121211034366

7. Lee EM, Jiménez-Fonseca P, Galán-Moral R, Coca-Membribes S, Fernández-Montes A, Sorribes E, et al. Toxicities and quality of life during cancer treatment in advanced solid tumors. Current Oncol. 2023 Oct 19;30(10):9205-16. https://doi.org/10.3390/curroncol30100665

8. Pearce S. Therapeutics the role of heterocycles in anti-cancer drug design [Internet]. Available from: https://www.cancer.gov/publica

9. Hossain M, Habib I, Singha K, Kumar A. FDA-approved heterocyclic molecules for cancer treatment: synthesis, dosage, mechanism of action and their adverse effect. Heliyon. 2024 Jan;10(1):e23172. https://doi.org/10.1016/j.heliyon.2023.e23172

10. Kumar Singh R. Key heterocyclic cores for smart anticancer drug-design. Bentham Book imprint. Singapure: Bentham Science Publishers Pte. Ltd.; 2022. https://doi.org/10.2174/97898150400431220201

11. Sampath Kumar HM, Herrmann L, Tsogoeva SB. Structural hybridization as a facile approach to new drug candidates. Bioorg Med Chem Lett. 2020 Dec;30(23):127514. https://doi.org/10.1016/j.bmcl.2020.127514

12. de Oliveira Pedrosa M, Duarte da Cruz RM, de Oliveira Viana J, de Moura RO, Ishiki HM, Barbosa Filho JM, et al. Hybrid compounds as direct multitarget ligands: a review. Curr Top Med Chem. 2017;9(17):1044-79. https://doi.org/10.2174/1568026616666160927160620

13. Moreno-Quintero G, Betancur-Zapata E, Herrera-Ramírez A, Cardona-Galeano W. New hybrid scaffolds based on 5-FU/curcumin: synthesis, cytotoxic, antiproliferative and pro-apoptotic effect. Pharmaceutics. 2023 Apr 12;15(4):1221. https://doi.org/10.3390/pharmaceutics15041221

14. Castrillón-López W, Herrera-Ramírez A, Moreno-Quintero G, Coa JC, Naranjo TW, Cardona-Galeano W. Resveratrol/hydrazone hybrids: synthesis and chemopreventive activity against colorectal cancer cells. Pharmaceutics. 2022 Oct 24;14(11):2278. https://doi.org/10.3390/pharmaceutics14112278

15. Moreno-Quintero G, Castrillón-Lopez W, Herrera-Ramirez A, Yepes- Pérez AF, Quintero-Saumeth J, Cardona-Galeano W. Synthesis and chemopreventive potential of 5-FU/genistein hybrids on colorectal cancer cells. Pharmaceuticals. 2022 Oct 21;15(10):1299. https://doi.org/10.3390/ph15101299

16. Cardona G W, Herrera R A, Castrillón L W, Ramírez Malule H. Chemistry and anticancer activity of hybrid molecules and derivatives based on 5-fluorouracil. Curr Med Chem. 2021 Sep 8;28(27):5551- 601. https://doi.org/10.2174/0929867328666210211164314

17. Singh RK, Kumar S, Prasad DN, Bhardwaj TR. Therapeutic journery of nitrogen mustard as alkylating anticancer agents: historic to future perspectives. Eur J Med Chem. 2018 May;151:401-33. https://doi.org/10.1016/j.ejmech.2018.04.001

18. Kumar A, Yadav AK, Mishra V, Kumar D. Recent advancements in triazole-based click chemistry in cancer drug discovery and development. SynOpen. 2023 May 17;07(02):186-208. https://doi.org/10.1055/s-0042-1751452

19. Kaur J, Saxena M, Rishi N. An overview of recent advances in biomedical applications of click chemistry. Bioconjug Chem. 2021 Aug 18;32(8):1455-71. https://doi.org/10.1021/acs.bioconjchem.1c00247

20. The Nobel Prize in Chemistry 2022. 2022. Available from: www.nobelprize.org/prizes/chemistry/2022/popular-information/

21. Khandelwal R, Vasava M, Abhirami RB, Karsharma M. Recent advances in triazole synthesis via click chemistry and their pharmacological applications: a review. Bioorg Med Chem Lett. 2024 Nov;112:129927. https://doi.org/10.1016/j.bmcl.2024.129927

22. Yu W , Lu X, Xiong L, Teng J, Chen C, Li B, et al. Thiol-ene click reaction in constructing liquid separation membranes for water treatment. Small. 2024 Jun 11;20(25). https://doi.org/10.1002/smll.202310799

23. Zhou H, Zhang X, Qu B, Zhao F, Man C, Jiang Y, et al. Biosensing meets click chemistry: a promising combination for analysis of food hazard factors. Coord Chem Rev. 2024 Dec;520:216137. https://doi.org/10.1016/j.ccr.2024.216137

24. Thirumurugan P, Matosiuk D, Jozwiak K. Click chemistry for drug development and diverse chemical-biology applications. Chem Rev. 2013 Jul 10;113(7):4905-79. https://doi.org/10.1021/cr200409f

25. Li X, Xiong Y. Application of “Click” chemistry in biomedical hydrogels. ACS Omega. 2022 Oct 25;7(42):36918-28. https://doi.org/10.1021/acsomega.2c03931

26. Zhao S, Liu J, Lv Z, Zhang G, Xu Z. Recent updates on 1,2,3-triazole-containing hybrids with in vivo therapeutic potential against cancers:aA mini-review. Eur J Med Chem. 2023 May;251:115254. https://doi.org/10.1016/j.ejmech.2023.115254

27. Mashayekh K, Shiri P. An overview of recent advances in the applications of click chemistry in the synthesis of bioconjugates with anticancer activities. ChemistrySelect. 2019 Dec 13;4(46):13459- 78. https://doi.org/10.1002/slct.201902362

28. van Eck NJ WL. Software survey: vOSviewer, a computer program for bibliometric mapping. 2010. https://doi.org/10.1007/s11192-009-0146-3

29. Dhiman A, Sharma R, Singh RK. Target-based anticancer indole derivatives and insight into structure-activity relationship: a mechanistic review update (2018-2021). Acta Pharm Sin B. 2022 Jul;12(7):3006-27. https://doi.org/10.1016/j.apsb.2022.03.021

30. Kumari A, Singh RK. Morpholine as ubiquitous pharmacophore in medicinal chemistry: deep insight into the structure-activity relationship (SAR). Bioorg Chem. 2020 Mar;96:103578. https://doi.org/10.1016/j.bioorg.2020.103578

31. Lizeth GR, Gustavo MQ, Angie HR, Wilson CL, Andrés FY, Wilson CG. New hybrid scaffolds based on ASA/genistein: synthesis, cytotoxic effect, molecular docking, drug-likeness, and in silico ADME/Tox modeling. J Appl Pharm Sci. 2022;12. https://doi.org/10.7324/JAPS.2021.120203

32. Krstulovi? L, Miškovi? Špoljari? K, Rastija V, Filipovi? N, Baji? M, Glavaš-Obrovac L. Novel 1,2,3-triazole-containing quinoline- benzimidazole hybrids: synthesis, antiproliferative activity, in silico ADME predictions, and docking. Molecules. 2023 Oct 6;28(19):6950. https://doi.org/10.3390/molecules28196950

33. Hou H, Qu B, Su C, Hou G, Gao F. Design, synthesis and anti-lung cancer evaluation of 1, 2, 3-triazole tethered dihydroartemisinin-isatin hybrids. Front Pharmacol. 2021 Dec 16;12. https://doi.org/10.3389/fphar.2021.801580

34. Djemoui A, Naouri A, Ouahrani MR, Djemoui D, Lahcene S, Lahrech MB, et al. A step-by-step synthesis of triazole-benzimidazole-chalcone hybrids: anticancer activity in human cells+. J Mol Struct. 2020 Mar;1204:127487. https://doi.org/10.1016/j.molstruc.2019.127487

35. Duan M, Mahal A, Mohammed B, Zhu Y, Tao H, Mai S, et al. Synthesis and antitumor activity of new tetrahydrocurcumin derivatives via click reaction. Nat Prod Res. 2022 Oct 18;36(20):5268-76. https://doi.org/10.1080/14786419.2021.1931181

36. Wu BW, Huang WJ, Liu YH, Liu QG, Song J, Hu T, et al. Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities. Eur J Med Chem. 2024 Feb;265:116118. https://doi.org/10.1016/j.ejmech.2023.116118

37. Mahmoud MA, Mohammed AF, Salem OIA, Almutairi TM, Bräse S, Youssif BGM. Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors. J Enzyme Inhib Med Chem. 2024 Dec 31;39(1):2305856. https://doi.org/10.1080/14756366.2024.2305856

38. Al-Qahtani SD, Al-Senani GM. Novel hybrid motifs of 2-(2-pyridinyl)-1H-benzo[d]imidazole-1,2,3-triazole: Synthesis, anticancer assessment, and in silico study. J Mol Struct. 2024 Dec;1318:139376. https://doi.org/10.1016/j.molstruc.2024.139376

39. de Souza AS, Dias DS, Ribeiro RCB, Costa DCS, de Moraes MG, Pinho DR, et al. Novel naphthoquinone-1H-1,2,3-triazole hybrids: design, synthesis and evaluation as inductors of ROS-mediated apoptosis in the MCF-7 cells. Bioorg Med Chem. 2024 Mar;102:117671. https://doi.org/10.1016/j.bmc.2024.117671

40. Abdel-Rahman AAH, El-Bayaa MN, Sobhy A, El-Ganzoury EM, Nossier ES, Awad HM, et al. Novel quinazolin-4-one based derivatives bearing 1,2,3-triazole and glycoside moieties as potential cytotoxic agents through dual EGFR and VEGFR-2 inhibitory activity. Sci Rep. 2024 Oct 23;14(1):24980. https://doi.org/10.1038/s41598-024-73171-8

41. Lavunuri S, Venkata Nadh R, Banothu D, Kumar Rapeti S. Synthesis of quinoline fused 1,2,3-triazole derivatives via continuous CuAAC and C H arylation; anti-breast cancer, anti-EGFR and HER2 activities, computational studies. Tetrahedron Lett. 2024 Oct;150:155282. https://doi.org/10.1016/j.tetlet.2024.155282

42. Nalla S, Aravind S, Annam SC, Padmavathi KV, Syed T, Subbarao M. Synthesis and biological evaluation of 1, 2, 3-triazole incorporated pyrrole derivatives as anticancer agents. Synth Commun. 2024 Nov 15;54(21):1828-41. https://doi.org/10.1080/00397911.2024.2408605

43. Narayanrao R, Ramachandra D, Ramdas D. Process for the preparation of rufinamide. WO2010043849A1. 2010.

44. Alshamari AK. Design and synthesis of novel 1,2,3-triazole levonorgestrel derivatives via click chemistry. Anticancer activity and molecular docking. Russian J Organ Chem. 2022 Dec 8;58(12):1878-88. https://doi.org/10.1134/S107042802212017X

45. Elganzory HH, Alminderej FM, El-Bayaa MN, Awad HM, Nossier ES, El-Sayed WA. Design, synthesis, anticancer activity and molecular docking of new 1,2,3-triazole-based glycosides bearing 1,3,4-thiadiazolyl, indolyl and arylacetamide scaffolds. Molecules. 2022 Oct 17;27(20):6960. https://doi.org/10.3390/molecules27206960

46. Alshamari AK. Anticancer activity and molecular docking of 1,2,3-triazole hybrids of phenol and 4-methoxy-2-methylphenyl: synthesis via click chemistry. Russian J Organ Chem. 2023 Mar 10;59(3):455-64. https://doi.org/10.1134/S1070428023030132

47. El Azab IH, El-Sheshtawy HS, Bakr RB, Elkanzi NAA. New 1,2,3-triazole-containing hybrids as antitumor candidates: design, click reaction synthesis, DFT calculations, and molecular docking study. Molecules. 2021 Jan 29;26(3):708. https://doi.org/10.3390/molecules26030708

48. Firoozpour L, Moghimi S, Fallah Barzegar MH, Toolabi M, Salarinejad S, Bijanzadeh HR, et al. Synthesis, molecular docking, and biological evaluation of pyridin-3-yl-pyrimidin-2-yl-triazole derivatives as anti-cancer agents. Polycycl Aromat Compd. 2024 Mar 15;44(3):2062-76. https://doi.org/10.1080/10406638.2023.2212101

49. Guo Y, Sang D, Guo B, Wang D, Xu X, Wang H, et al. Synthesis and biological evaluation of novel 1,2,3-triazole hybrids of cabotegravir: identification of potent antitumor activity against lung cancer. Front Pharmacol. 2023 Sep 20;14:1265245. https://doi.org/10.3389/fphar.2023.1265245

50. El-Sheref EM, Elbastawesy MAI, Brown AB, Shawky AM, Gomaa HAM, Bräse S, et al. Design and synthesis of (2-oxo-1,2- Dihydroquinolin-4-yl)-1,2,3-triazole derivatives via click reaction: potential apoptotic antiproliferative agents. Molecules. 2021 Nov 10;26(22):6798. https://doi.org/10.3390/molecules26226798

51. Salameh BA, Abu-Safieh KA, Al-Hushki EH, Talib WH, Al-ataby IA, Al-Qawasmeh RA. New maleimide 1,2,3-triazole hybrids: design, synthesis, anticancer, and antimicrobial activities. Monatshefte für Chemie Chem Monthly. 2020 Oct 8;151(10):1609-19. https://doi.org/10.1007/s00706-020-02685-4

52. de O. Torres NMP, Cardoso G de A, Silva H, de Freitas RP, Alves RB. New purine-triazole hybrids as potential anti-breast cancer agents: synthesis, antiproliferative activity, and ADMET in silico study. Med Chem Res. 2023 Aug 6;32(8):1816-31. https://doi.org/10.1007/s00044-023-03115-w

53. Hadiyal SD, Lalpara JN, Parmar ND, Joshi HS. Microwave irradiated targeted synthesis of pyrrolobenzodiazepine embrace 1,2,3-triazole by click chemistry synthetic aspect and evaluation of anticancer and antimicrobial activity. Polycycl Aromat Compd. 2022 Aug 9;42(7):4752-68. https://doi.org/10.1080/10406638.2021.1913425

54. Oggu S, Akshinthala P, Katari NK, Nagarapu LK, Malempati S, Gundla R, et al. Design, synthesis, anticancer evaluation and molecular docking studies of 1,2,3-triazole incorporated 1,3,4-oxadiazole- Triazine derivatives. Heliyon. 2023 May;9(5):e15935. https://doi.org/10.1016/j.heliyon.2023.e15935

55. Duan M, Mahal A, Alkouri A, Wang C, Zhang Z, Ren J, et al. Synthesis, anticancer activity, and molecular docking of new 1,2,3-triazole linked tetrahydrocurcumin derivatives. Molecules. 2024 Jun 25;29(13):3010. https://doi.org/10.3390/molecules29133010

56. Das VB, Poojary B, Kamat V, Hamzad S, Suman P. Synthesis, anticancer evaluation, and molecular docking study of 1,2,3-triazole-containing hydrazones as potential HER2 Kinase inhibitors. Russian J Organ Chem. 2024 Mar 19;60(3):502-12. https://doi.org/10.1134/S1070428024030199

57. Gao E, Wang Y, Fan G lu, Xu G, Wu ZY, Liu ZJ, et al. Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation. Sci Rep. 2024 Apr 22;14(1):9223. https://doi.org/10.1038/s41598-024-60000-1

58. Elsebaie HA, Abdulla MH, Elsayed ZM, Shaldam MA, Tawfik HO, Morsy SN, et al. Unveiling the potential of isatin-grafted phenyl- 1,2,3-triazole derivatives as dual VEGFR-2/STAT-3 inhibitors: design, synthesis and biological assessments. Bioorg Chem. 2024 Oct;151:107626. https://doi.org/10.1016/j.bioorg.2024.107626

Article Metrics
43 Views 27 Downloads 70 Total

Year

Month

Related Search

By author names