European Journal of Chemistry 2022, 13(3), 307-318 | doi: https://doi.org/10.5155/eurjchem.13.3.307-318.2282 | Get rights and content

Issue cover




Crossmark

  Open Access OPEN ACCESS | Open Access PEER-REVIEWED | RESEARCH ARTICLE | DOWNLOAD PDF | VIEW FULL-TEXT PDF | TOTAL VIEWS

iNOS inhibitors: Benzimidazole-coumarin derivatives to combat inflammation


Richa Minhas (1) orcid , Yogita Bansal (2,*) orcid

(1) Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002 India
(2) Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002 India
(*) Corresponding Author

Received: 22 Apr 2022 | Revised: 15 Jun 2022 | Accepted: 19 Jun 2022 | Published: 30 Sep 2022 | Issue Date: September 2022

Abstract


Inducible nitric oxide synthase (iNOS) plays an important role in the inflammatory processes via accelerating the production of nitric oxide (NO). The efforts to develop small molecules as selective inhibitors of iNOS are being reported across the globe. The current study explores varied benzimidazole-coumarin derivatives as anti-iNOS agents. Literature survey suggests 2-aminobenzimidazole, coumarin nucleus, and 4-atom linker as important structural components for iNOS inhibition. Target compounds were designed and synthesized by coupling 2-aminobenzimidazole with (un)substituted coumarin through different linkers. These were docked in iNOS (1QW4) and nNOS (1QW6) targets to ascertain their iNOS selectivity, and evaluated for NO and iNOS inhibitory activities in vitro. The most active inhibitors were subsequently evaluated for acute toxicity and anti-inflammatory activity using carrageenan-induced rat paw edema model in vivo. All compounds possessed moderate to good NO and iNOS inhibitory activities. Compounds 14a, 14b, 14d, and 14e were the most potent inhibitors in vitro. These were found to significantly reduce the inflammation. Compounds 14d and 14e have been identified as the most potent iNOS inhibitors to combat inflammation. These derivatives may serve as potential compounds as such against iNOS, or as leads for the development of novel anti-iNOS agents.


Announcements


Our editors have decided to support scientists to publish their manuscripts in European Journal of Chemistry without any financial constraints.

1- The article processing fee will not be charged from the articles containing the single-crystal structure characterization between November 15, 2022 and December 28, 2022 (Voucher code: SINGLE2022).

2. Young writers will not be charged for the article processing fee between November 15, 2022 and December 28, 2022 (Voucher code: YOUNG2022).

3. The article processing fee will not be charged from the articles containing a part of the PhD thesis between November 15, 2022 and December 28, 2022 (Voucher code: PhD2022).

4. The article processing fee will not be charged from authors who have at least one publication in the European Journal of Chemistry between November 15, 2022 and December 28, 2022 (Voucher code: (Voucher code: AUTHOR2022).

Editor-in-Chief

European Journal of Chemistry

Keywords


Docking; Coumarin; Carrageenan; Inflammation; Benzimidazole; Biological activity

Full Text:

PDF
PDF    Open Access

DOI: 10.5155/eurjchem.13.3.307-318.2282

Links for Article


| | | | | |

| | | | | | |

| | | |

Related Articles




Article Metrics

icon graph This Abstract was viewed 136 times | icon graph PDF Article downloaded 47 times

Funding information


Department of Science and Technology, Ministry of Science and Technology, India.

References


[1]. Kahlenberg, J. M.; Fox, D. A. Advances in the medical treatment of rheumatoid arthritis. Hand Clin. 2011, 27, 11-20.
https://doi.org/10.1016/j.hcl.2010.09.002

[2]. Handa, R.; Rao, U. R. K.; Lewis, J. F. M.; Rambhad, G.; Shiff, S.; Ghia, C. J. Literature review of rheumatoid arthritis in India. Int. J. Rheum. Dis. 2016, 19, 440-451.
https://doi.org/10.1111/1756-185X.12621

[3]. Upadhyay, K.; Bavishi, A.; Thakrar, S.; Radadiya, A.; Vala, H.; Parekh, S.; Bhavsar, D.; Savant, M.; Parmar, M.; Adlakha, P.; Shah, A. Synthesis and biological evaluation of 4-styrylcoumarin derivatives as inhibitors of TNF-α and IL-6 with anti-tubercular activity. Bioorg. Med. Chem. Lett. 2011, 21, 2547-2549.
https://doi.org/10.1016/j.bmcl.2011.02.016

[4]. Abdelazeem, A. H.; Khan, S. I.; White, S. W.; Sufka, K. J.; McCurdy, C. R. Design, synthesis and biological evaluation of bivalent benzoxazolone and benzothiazolone ligands as potential anti-inflam-matory/ analgesic agents. Bioorg. Med. Chem. 2015, 23, 3248-3259.
https://doi.org/10.1016/j.bmc.2015.04.057

[5]. Cinelli, M. A.; Do, H. T.; Miley, G. P.; Silverman, R. B. Inducible nitric oxide synthase: Regulation, structure, and inhibition Med. Res. Rev. 2020, 40, 158-189.
https://doi.org/10.1002/med.21599

[6]. Minhas, R.; Bansal, Y.; Bansal, G. Inducible nitric oxide synthase inhibitors: A comprehensive update. Med. Res. Rev. 2020, 40, 823-855.
https://doi.org/10.1002/med.21636

[7]. Kadhum, A. A. H.; Al-Amiery, A. A.; Musa, A. Y.; Mohamad, A. B. The antioxidant activity of new coumarin derivatives. Int. J. Mol. Sci. 2011, 12, 5747-5761.
https://doi.org/10.3390/ijms12095747

[8]. Kostova, I. Synthetic and natural coumarins as antioxidants. Mini Rev. Med. Chem. 2006, 6, 365-374.
https://doi.org/10.2174/138955706776361457

[9]. Minhas, R.; Bansal, Y. Inhibition of iNOS by benzimidazole derivatives: Synthesis, docking, and biological evaluations. Med. Chem. 2022, 18, 602-615.
https://doi.org/10.2174/1573406417666210927123137

[10]. Maestro- Schrödinger Release 2022-2: Maestro, Schrödinger, LLC, New York, NY, 2021.

[11]. Ahluwalia, V. K.; Bhagat, P.; Aggarwal, R.; Chandra, R. Intermediates for organic synthesis; I. K. International Publishing House: New Delhi, India, 2005.

[12]. ChemBioDraw Ultra 12.0. CambridgeSoft, 100 Cambridge Park Drive, Cambridge, MA 02140. www.cambridgesoft.com (accessed June 17, 2022).

[13]. LigPrep - Schrödinger Release 2022-2: LigPrep, Schrödinger, LLC, New York, NY, 2021.

[14]. Kaminski, G. A.; Friesner, R. A.; Tirado-Rives, J.; Jorgensen, W. J. Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides. J. Phys. Chem. B 2001, 105 (28), 6474-6487.
https://doi.org/10.1021/jp003919d

[15]. RCSB Protein Data Bank RCSB PDB: Homepage. https://www.rcsb.org/ (accessed June 17, 2022).

[16]. QikProp - Schrödinger Release 2022-2: QikProp, Schrödinger, LLC, New York, NY, 2021.

[17]. Mishra, T.; Bhatia, A. Augmentation of expression of immunocytes' functions by seed extract of Ziziphusmauritiana (Lamk.). J. Ethnopharmacol. 2010, 127, 341-345.
https://doi.org/10.1016/j.jep.2009.10.033

[18]. Minhas, R.; Bansal, G.; Bansal, Y. Novel coupled molecules from active structural motifs of synthetic and natural origin as immunosuppressants. Med. Chem. 2020, 16, 544-554.
https://doi.org/10.2174/1573406415666190409111459

[19]. OECD guidelines for the testing of chemicals - section 4: Health effects: Test no. 425: Acute oral toxicity: Up-and-down procedure; Organisation for Economic Co-Operation and Development, 2014.

[20]. Salvemini, D.; Wang, Z.-Q.; Wyatt, P. S.; Bourdon, D. M.; Marino, M. H.; Manning, P. T.; Currie, M. G. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br. J. Pharmacol. 1996, 118, 829-838.
https://doi.org/10.1111/j.1476-5381.1996.tb15475.x

[21]. GraphPad Prism version 8.0.0 for Windows, GraphPad Software, San Diego, California USA, www.graphpad.com. (accessed June 17, 2022).

[22]. Jackson, S. A.; Sahni, S.; Lee, L.; Luo, Y.; Nieduzak, T. R.; Liang, G.; Chiang, Y.; Collar, N.; Fink, D.; He, W.; Laoui, A.; Merrill, J.; Boffey, R.; Crackett, P.; Rees, B.; Wong, M.; Guilloteau, J.-P.; Mathieu, M.; Rebello, S. S. Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase. Bioorg. Med. Chem. 2005, 13, 2723-2739.
https://doi.org/10.1016/j.bmc.2005.02.036

[23]. Singh, M.; Silakari, O. Design, synthesis and biological evaluation of novel 2-phenyl-1-benzopyran-4-one derivatives as potential poly-functional anti-Alzheimer's agents. RSC Adv. 2016, 6, 108411-108422.
https://doi.org/10.1039/C6RA17678J

[24]. Silverstein, R. M.; Webster, F. X.; Kiemle, D. J. The spectrometric identification of organic compounds; 7th ed.; John Wiley & Sons: Nashville, TN, 2005.

[25]. Carrión, M. D.; López Cara, L. C.; Camacho, M. E.; Tapias, V.; Escames, G.; Acuña-Castroviejo, D.; Espinosa, A.; Gallo, M. A.; Entrena, A. Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and iNOS) potential inhibitors (III). Eur. J. Med. Chem. 2008, 43, 2579-2591.
https://doi.org/10.1016/j.ejmech.2008.01.014

[26]. Annunziata, F.; Pinna, C.; Dallavalle, S.; Tamborini, L.; Pinto, A. An overview of coumarin as a versatile and readily accessible scaffold with broad-ranging biological activities. Int. J. Mol. Sci. 2020, 21, 4618.
https://doi.org/10.3390/ijms21134618


How to cite


Minhas, R.; Bansal, Y. Eur. J. Chem. 2022, 13(3), 307-318. doi:10.5155/eurjchem.13.3.307-318.2282
Minhas, R.; Bansal, Y. iNOS inhibitors: Benzimidazole-coumarin derivatives to combat inflammation. Eur. J. Chem. 2022, 13(3), 307-318. doi:10.5155/eurjchem.13.3.307-318.2282
Minhas, R., & Bansal, Y. (2022). iNOS inhibitors: Benzimidazole-coumarin derivatives to combat inflammation. European Journal of Chemistry, 13(3), 307-318. doi:10.5155/eurjchem.13.3.307-318.2282
Minhas, Richa, & Yogita Bansal. "iNOS inhibitors: Benzimidazole-coumarin derivatives to combat inflammation." European Journal of Chemistry [Online], 13.3 (2022): 307-318. Web. 3 Dec. 2022
Minhas, Richa, AND Bansal, Yogita. "iNOS inhibitors: Benzimidazole-coumarin derivatives to combat inflammation" European Journal of Chemistry [Online], Volume 13 Number 3 (30 September 2022)

The other citation formats (EndNote | Reference Manager | ProCite | BibTeX | RefWorks) for this article can be found online at: How to cite item



DOI Link: https://doi.org/10.5155/eurjchem.13.3.307-318.2282


CrossRef | Scilit | GrowKudos | Researchgate | Publons | ScienceGate | Scite | Lens | OUCI

WorldCat Paperbuzz | LibKey Citeas | Dimensions | Semanticscholar | Plumx | Kopernio | Zotero | Mendeley

ZoteroSave to Zotero MendeleySave to Mendeley



European Journal of Chemistry 2022, 13(3), 307-318 | doi: https://doi.org/10.5155/eurjchem.13.3.307-318.2282 | Get rights and content

Refbacks

  • There are currently no refbacks.




Copyright (c) 2022 Authors

Creative Commons License
This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).



© Copyright 2010 - 2022  Atlanta Publishing House LLC All Right Reserved.

The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.

Copyright 2010-2022 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 2850 Smith Ridge Trce Peachtree Cor GA 30071-2636, USA. Registered in USA.