Author(s):
Renu, Shilpa, Sanjiv Duggal
Email(s):
somasharma378@gmail.com
DOI:
10.52711/0974-4150.2025.00035
Address:
Renu, Shilpa, Sanjiv Duggal
Global College of Pharmacy, Kahnpur Khui, Anandpur Sahib, Punjab, India, 140117.
*Corresponding Author
Published In:
Volume - 18,
Issue - 4,
Year - 2025
ABSTRACT:
A tumor represents a multifaceted disease characterized by the unrestrained growth of abnormal cells and their spread to different regions of the body. This disease can originate in almost any organ or tissue within the body. It is a leading global health challenge, causing one in six deaths worldwide. It can be prevented by raising awareness of the fundamental causes of the disease and its risk factors. Despite significant progress in advanced treatments like immunotherapy, targeted therapies, stem cell transplantation, precision medicine, hormonal treatments, palliative care, and traditional methods like chemotherapy and radiation therapy, effective cancer management remains difficult. Numerous benzimidazole scaffolds have gained significant interest for their powerful role in advancing cancer treatments, due to their wide range of biological effects and promising therapeutic potential, among other anticancer medications found in recent years. These findings highlight benzimidazole's significant promise as a versatile molecular platform for developing innovative therapeutic interventions across diverse medical disciplines.
Cite this article:
Renu, Shilpa, Sanjiv Duggal. Cancer: A Multifaceted Disease and Therapeutic Potential of Benzimidazole as Anticancer Agents. Asian Journal of Research in Chemistry.2025; 18(4):228-4. doi: 10.52711/0974-4150.2025.00035
Cite(Electronic):
Renu, Shilpa, Sanjiv Duggal. Cancer: A Multifaceted Disease and Therapeutic Potential of Benzimidazole as Anticancer Agents. Asian Journal of Research in Chemistry.2025; 18(4):228-4. doi: 10.52711/0974-4150.2025.00035 Available on: https://ajrconline.org/AbstractView.aspx?PID=2025-18-4-4
REFERENCES:
1. Magalhaes LG, Ferreira LL, Andricopulo AD. Recent advances and perspectives in cancer drug design. Anais da Academia Brasileira de Ciências. 2018 May 14;90(1 Suppl 2):1233-50. DOI:10.1590/0001 3765201820170823
2. Kaleem M, Perwaiz M, Nur SM, Abdulrahman AO, Ahmad W, Al-Abbasi FA, Kumar V, Kamal MA, Anwar F. Epigenetics of triple-negative breast cancer via natural compounds. Current Medicinal Chemistry. 2022 Mar 1;29(8):1436-58. DOI: 10.2174/0929867328666210707165530
3. Karn V, Sandhya S, Hsu W, Parashar D, Singh HN, Jha NK, Gupta S, Dubey NK, Kumar S. CRISPR/Cas9 system in breast cancer therapy: advancement, limitations and future scope. Cancer cell international. 2022 Jul 25;22(1): 234.DOI: 10.1186/s12935-022-02654-3
4. Chunarkar-Patil P, Kaleem M, Mishra R, Ray S, Ahmad A, Verma D, Bhayye S, Dubey R, Singh HN, Kumar S. Anticancer drug discovery based on natural products: From computational approaches to clinical studies. Biomedicines. 2024 Jan 16;12(1):201. DOI: 10.3390/biomedicines12010201
5. Toporcov TN, Wünsch Filho V. Epidemiological science and cancer control. Clinics. 2018 Sep 21;73: e627s. DOI: 10.6061/clinics/2018/e627s
6. Weir HK, Thompson TD, Stewart SL, White MC. Cancer incidence projections in the United States between 2015 and 2050. Preventing chronic disease. 2021 Jun 10;18: E59. DOI: http://dx.doi.org/10.5888/pcd18.210006
7. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global cancer observatory: cancer today. Lyon: International agency for research on cancer.2020 Nov 25;20182020. Available from: https://gco.iarc.fr/today.
8. Wright JB. The chemistry of the benzimidazoles. Chemical reviews. 1951 Jun 1;48(3):397-541. DOI: https://doi.org/10.1021/cr60151a002
9. Debus H. Ueber die einwirkung des ammoniaks auf glyoxal. Justus Liebigs Annalen der Chemie. 1858;107(2):199-208. DOI:https://doi.org/10.1002/jlac.18581070209
10. Hobrecker F. Ueber reductionsprodukte der nitracetamidverbindungen. Berichte der deutschen chemischen Gesellschaft. 1872 Jul;5(2):920-4. DOI: https://doi.org/10.1002/ cber.18720050295
11. Mehra A, Sangwan R. Synthesis and pharmacological properties of the benzimidazole scaffold: a patent review. ChemistrySelect. 2023 Dec 5;8(45): e202300537. DOI:10.1002/slct.202300537
12. Gajanan G, Shital S, Vipul T, Babar V, Dnyaneshwar J, Vaibhav D, Vaibhav C. A Review on Benzimidazole and it’s Biological Activities. Journal of Pharmaceutical Chemistry and Drug Formulation. 2021;3(1). DOI: https://www.researchgate.net/publication/349812021
13. Tahlan S, Ramasamy K, Lim SM, Shah SA, Mani V, Narasimhan B. 4-(2-(1 H-Benzo [d] imidazol-2-ylthio) acetamido)-N-(substituted phenyl) benzamides: design, synthesis and biological evaluation. BMC chemistry. 2019 Dec; 13:1-6. DOI:https://doi.org/10.1186/s13065-019-0533-7
14. Gu W, Miao TT, Hua DW, Jin XY, Tao XB, Huang CB, Wang SF. Synthesis and in vitro cytotoxic evaluation of new 1H-benzo [d] imidazole derivatives of dehydroabietic acid. Bioorganic & medicinal chemistry letters. 2017 Mar 1;27(5):1296-300. DOI: 10.1016/j.bmcl.2017.01.028
15. Mook Jr RA, Ren XR, Wang J, Piao H, Barak LS, Lyerly HK, Chen W. Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis. Bioorganic & medicinal chemistry. 2017 Mar 15;25(6):1804-16. DOI: 10.1016/j.bmc.2017.01.046
16. Shao KP, Zhang XY, Chen PJ, Xue DQ, He P, Ma LY, Zheng JX, Zhang QR, Liu HM. Synthesis and biological evaluation of novel pyrimidine–benzimidazol hybrids as potential anticancer agents. Bioorganic & medicinal chemistry letters. 2014 Aug 15;24(16):3877-81. DOI: 10.1016/j.bmcl.2014.06.050
17. Pilch DS, Xu Z, Sun Q, LaVoie EJ, Liu LF, Breslauer KJ. A terbenzimidazole that preferentially binds and conformationally alters structurally distinct DNA duplex domains: a potential mechanism for topoisomerase I poisoning. Proceedings of the National Academy of Sciences. 1997 Dec 9;94(25):13565-70.
18. Kim JS, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ. Substituted 2, 5 ‘-Bi-1 H-benzimidazoles: Topoisomerase I Inhibition and Cytotoxicity. Journal of Medicinal Chemistry. 1996 Feb 16;39(4):992-8. DOI: 10.1021/jm950412w
19. Bansal S, Sur S, Tandon V. Benzimidazoles: Selective inhibitors of topoisomerase I with differential modes of action. Biochemistry. 2018 Dec 26;58(6):809-17. DOI:https://doi.org/10.1021/acs.biochem.8b01102
20. Issar U, Arora R, Kumari T, Kakkar R. Combined pharmacophore-guided 3D-QSAR, molecular docking, and virtual screening on bis-benzimidazoles and ter-benzimidazoles as DNA–topoisomerase I poisons. Structural Chemistry. 2019 Aug 15; 30:1185-201. DOI: https://doi.org/10.1007/s11224-018-1257-3
21. Hranjec M, Pavlovic G, Marjanovic M, Kralj M, Karminski-Zamloa G. Benzimidazole derivatives related to 2,3-acrylonitriles, benzimidazo [1, 2-a] quinolines and fluorenes: synthesis, antitumor evaluation in vitro and crystal strucuture determination. European journal of medicinal chemistry. 2010 Jun 1;45(6):2405-17. DOI: https://doi.org/10.1016/j.ejmech.2010.02.022
22. Yoon YK, Ali MA, Wei AC, Shirazi AN, Parang K, Choon TS. Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. European journal of medicinal chemistry. 2014 Aug 18;83: 448-54.DOI: 10.1016/j.ejmech.2014.06.060
23. Singh M, Tandon V. Synthesis and biological activity of novel inhibitors of topoisomerase I: 2-Aryl-substituted 2-bis-1H-benzimidazoles. European journal of medicinal chemistry. 2011 Feb 1;46(2):659-69. DOI: 10.1016/j.ejmech.2010.11.046
24. Wang YT, Qin YJ, Yang N, Zhang YL, Liu CH, Zhu HL. Synthesis, biological evaluation, and molecular docking studies of novel 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as potential tubulin polymerization inhibitors. European journal of medicinal chemistry. 2015 Jun 24; 99:125-37. DOI: 10.1016/j.ejmech.2015.05.021
25. Zhang YL, Yang R, Xia LY, Man RJ, Chu YC, Jiang AQ, Wang ZC, Zhu HL. Synthesis, anticancer activity and molecular docking studies on 1,2-diarylbenzimidazole analogues as anti-tubulin agents. Bioorganic Chemistry. 2019 Nov 1; 92:103219. DOI: https://Doi. org/10.1016/j.bioorg.2019.103219
26. Baig MF, Nayak VL, Budaganaboyina P, Mullagiri K, Sunkari S, Gour J, Kamal A. Synthesis and biological evaluation of imidazo [2, 1-b] thiazole-benzimidazole conjugates as microtubule-targeting agents. Bioorganic Chemistry. 2018 Apr 1; 77:515-26. DOI: https://doi.org/ 10.1016/j.bioorg.2018.02.005
27. Panchal I, Devgirkar AG, Patel AD, Nagani A, Lad C. Molecular modelling, synthesis and biological evaluation of novel benzimidazole derivatives for the treatment of breast cancer. Current Chinese Chemistry.2021 Mar;1(1):11-20. DOI: https://doi.org/10.2174/ 2666001601666200121163605
28. Akhtar MJ, Khan AA, Ali Z, Dewangan RP, Rafi M, Hassan MQ, Akhtar MS, Siddiqui AA, Partap S, Pasha S, Yar MS. Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors. Bioorganic Chemistry. 2018 Aug 1; 78:158-69. DOI: https://doi.org/ 10.1016/j.bioorg.2018.03.002
29. Delaney S, Pascaly M, Bhattacharya PK, Han K, Barton JK. Oxidative damage by ruthenium complexes containing the dipyridophenazine ligand or its derivatives: a focus on intercalation. Inorganic chemistry. 2002 Apr 8;41(7):1966-74. DOI:https://doi.org/10.1021/ic0111738
30. Demirayak S, Kayagil I, Yurttas L. Microwave supported synthesis of some novel 1, 3-Diarylpyrazino [1, 2-a] benzimidazole derivatives and investigation of their anticancer activities. European journal of medicinal chemistry. 2011 Jan 1;46(1):411-6. DOI: https://doi.org/10.1016/j.ejmech.2010.11.007
31. Rajendar P, Srinivasadesikan V, Tripuramallu BK. Synthesis and biological evolution of aryl quinolin-benzimidazole-1, 2, 3-triazole as anticancer agents. Chemical Data Collections. 2023 Jun 1; 45:101008. DOI:https://doi.org/10.1016/j.cdc.2023. 101008
32. Gao C, Li B, Zhang B, Sun Q, Li L, Li X, Chen C, Tan C, Liu H, Jiang Y. Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents. bioorganic & medicinal chemistry. 2015 Apr 15;23(8):1800-7. DOI: https://doi.org/10. 1016/j.bmc.2015.02.036
33. Sharma P, Reddy TS, Thummuri D, Senwar KR, Kumar NP, Naidu VG, Bhargava SK, Shankaraiah N. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents. European journal of medicinal chemistry. 2016 Nov 29; 124:608-21. DOI:https:// doi. org/ 10. 1016/j. ejmech. 2016.08.029
34. Goud NS, Ghouse SM, Vishnu J, Komal D, Talla V, Alvala R, Pranay J, Kumar J, Qureshi IA, Alvala M. Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents. Bioorganic Chemistry. 2019 Aug 1; 89:103016. DOI:https:// doi. org/ 10. 1016/j. bioorg. 2019. 103016
35. Acar Çevik U, Celik I, Işık A, Ahmad I, Patel H, Özkay Y, Kaplancıklı ZA. Design, synthesis, molecular modeling, DFT, ADME and biological evaluation studies of some new 1, 3, 4-oxadiazole linked benzimidazoles as anticancer agents and aromatase inhibitors. Journal of Biomolecular Structure and Dynamics. 2023 Mar 24;41(5):1944-58. DOI: https://doi. org/10.1080/ 07391102.2022.2025906
36. Husain A, Bhutani M, Parveen S, Khan SA, Ahmad A, Iqbal MA. Synthesis, in vitro cytotoxicity, ADME, and molecular docking studies of benzimidazole‐bearing furanone derivatives. Journal of the Chinese Chemical Society. 2021 Feb;68(2):362-73. DOI:https://doi.org/10.1002/jccs.202000130
37. Tishler RB, Lamppu DM, Park S, Price BD. Microtubule-active drugs taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53. Cancer Research. 1995 Dec 15;55(24):6021-5.
38. Chou S, Ercolani RJ, Derakhchan K. Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus. Antiviral research. 2018 Sep 1; 157:128-33 DOI: 10.1016/j.antiviral.2018.07.013