Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation
-
Zafer Sahin
,
Yağmur Özhan
,
Hande Sipahi
,
Sevde Nur Biltekin
,
Leyla Yurttaş
,
Barkin Berk
and
Şeref Demirayak
Abstract
Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1H NMR, 13C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC50. Rest of the compounds (1, 3–9) showed 10.4–28.1 μM IC50 on COX-2 and 17.0–35.6 μM IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1–9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds (1–9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.
-
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
-
Research funding: None declared.
-
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
References
1. Ian Todd, GS, Fairclough, L. Immunology: lecture notes. New York: John Wiley & Sons; 2015.Search in Google Scholar
2. Netea, MG, Balkwill, F, Chonchol, M, Cominelli, F, Donath, MY, Giamarellos-Bourboulis, EJ, et al.. A guiding map for inflammation. Nat Immunol 2017;18:826–31. https://doi.org/10.1038/ni.3790.Search in Google Scholar
3. Kurumbail, RG, Kiefer, JR, Marnett, LJ. Cyclooxygenase enzymes: catalysis and inhibition. Curr Opin Struct Biol 2001;11:752–60. https://doi.org/10.1016/s0959-440x(01)00277-9.Search in Google Scholar
4. Shrivastava, SK, Srivastava, P, Bandresh, R, Tripathi, PN, Tripathi, A. Design, synthesis, and biological evaluation of some novel indolizine derivatives as dual cyclooxygenase and lipoxygenase inhibitor for anti-inflammatory activity. Bioorg Med Chem 2017;25:4424–32. https://doi.org/10.1016/j.bmc.2017.06.027.Search in Google Scholar PubMed
5. Norregaard, R, Kwon, TH, Frokiaer, J. Physiology and pathophysiology of cyclooxygenase-2 and prostaglandin E2 in the kidney. Kidney Res Clin Pract 2015;34:194–200. https://doi.org/10.1016/j.krcp.2015.10.004.Search in Google Scholar PubMed PubMed Central
6. Taciak, B, Bialasek, M, Braniewska, A, Sas, Z, Sawicka, P, Kiraga, L, et al.. Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages. PLoS One 2018;13:e0198943. https://doi.org/10.1371/journal.pone.0198943.Search in Google Scholar PubMed PubMed Central
7. Karadag, AE, Demirci, B, Caskurlu, A, Demirci, F, Okur, ME, Orak, D, et al.. In vitro antibacterial, antioxidant, anti-inflammatory and analgesic evaluation of Rosmarinus officinalis L. flower extract fractions. South Afr J Bot 2019;125:214–20.10.1016/j.sajb.2019.07.039Search in Google Scholar
8. Gao, Y, Jiang, W, Dong, C, Li, C, Fu, X, Min, L, et al.. Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-kappaB and MAPKs signaling pathways. Toxicol Vitro 2012;26:1–6. https://doi.org/10.1016/j.tiv.2011.09.019.Search in Google Scholar PubMed
9. Lee, JY, Park, W. Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinic-polycytidylic acid. Molecules 2011;16:7132–42. https://doi.org/10.3390/molecules16087132.Search in Google Scholar PubMed PubMed Central
10. Brogden, RN. Pyrazolone derivatives. Drugs 1986;32:60–70. https://doi.org/10.2165/00003495-198600324-00006.Search in Google Scholar PubMed
11. Biava, M. Introduction to COX inhibitors. Future Med Chem 2018;10:1737–40. https://doi.org/10.4155/fmc-2018-0159.Search in Google Scholar PubMed
12. El Sayed, MT, El-Sharief, M, Zarie, ES, Morsy, NM, Elsheakh, AR, Voronkov, A, et al.. Design, synthesis, anti-inflammatory activity and molecular docking of potential novel antipyrine and pyrazolone analogs as cyclooxygenase enzyme (COX) inhibitors. Bioorg Med Chem Lett 2018;28:952–7. https://doi.org/10.1016/j.bmcl.2018.01.043.Search in Google Scholar PubMed
13. Farag, AA, El Shehry, MF, Abbas, SY, Abd-Alrahman, SN, Atrees, AA, Al-basheer, HZ, et al.. Synthesis of pyrazoles containing benzofuran and trifluoromethyl moieties as possible anti-inflammatory and analgesic agents. Z Naturforsch B Chem Sci 2015;70:519–26. https://doi.org/10.1515/znb-2015-0009.Search in Google Scholar
14. Ragab, FA, Eid, NM, Hassan, GS, Nissan, YM. Synthesis and anti-inflammatory activity of some benzofuran and benzopyran-4-one derivatives. Chem Pharm Bull 2012;60:110–20. https://doi.org/10.1248/cpb.60.110.Search in Google Scholar PubMed
15. Hu, ZF, Chen, LL, Qi, J, Wang, YH, Zhang, H, Yu, BY. Two new benzofuran derivatives with anti-inflammatory activity from Liriope spicata var. prolifera. Fitoterapia 2011;82:190–2. https://doi.org/10.1016/j.fitote.2010.09.002.Search in Google Scholar PubMed
16. FitzGerald, GA, Patrono, C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001;345:433–42. https://doi.org/10.1056/nejm200108093450607.Search in Google Scholar PubMed
17. Riendeau, D, Percival, MD, Brideau, C, Charleson, S, Dube, D, Ethier, D, et al.. Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Therapeut 2001;296:558–66.Search in Google Scholar
18. Okur, ME, Karadag, AE, Ustundag Okur, N, Ozhan, Y, Sipahi, H, Ayla, S, et al.. In vivo wound healing and in vitro anti-inflammatory activity evaluation of Phlomis russeliana extract gel formulations. Molecules 2020;25:2695. https://doi.org/10.3390/molecules25112695.Search in Google Scholar PubMed PubMed Central
19. Abe, K, Itoyama, Y, Sobue, G, Tsuji, S, Aoki, M, Doyu, M, et al.. Edaravone, Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degeneration 2014;15:610–7. https://doi.org/10.3109/21678421.2014.959024.Search in Google Scholar PubMed PubMed Central
20. Kaur, A, Wakode, S, Pathak, DP, Sharma, V, Shakya, AK. Synthesis, cyclooxygenase-2 inhibition, anti-inflammatory evaluation and docking study of substituted-N-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives. Med Chem 2018;14:660–73. https://doi.org/10.2174/1573406414666180322091832.Search in Google Scholar PubMed
21. Sahin, Z, Biltekin, SN, Yurttas, L, Berk, B, Ozhan, Y, Sipahi, H, et al.. Novel cyanothiouracil and cyanothiocytosine derivatives as concentration-dependent selective inhibitors of U87MG glioblastomas: adenosine receptor binding and potent PDE4 inhibition. Eur J Med Chem 2021;212:113125. https://doi.org/10.1016/j.ejmech.2020.113125.Search in Google Scholar PubMed PubMed Central
22. Okur, ME, Karadag, AE, Ozhan, Y, Sipahi, H, Ayla, S, Daylan, B, et al.. Anti-inflammatory, analgesic and in vivo-in vitro wound healing potential of the Phlomis rigida Labill. extract. J Ethnopharmacol 2021;266:113408. https://doi.org/10.1016/j.jep.2020.113408.Search in Google Scholar PubMed
23. Erdoğan, M, Konya, R, Özhan, Y, Sipahi, H, Çinbilgel, İ, Masullo, M, et al.. Secondary metabolites from Scutellaria brevibracteata subsp. subvelutina and their in vitro anti-inflammatory activities. South Afr J Bot 2021;139:12–8.10.1016/j.sajb.2021.01.028Search in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/ZNC-2021-0217).
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Research Articles
- In vitro anticancer and antibacterial potentials of selected medicinal plants and isolation and characterization of a natural compound from Withania coagulans
- New compounds from Sarcophyton glaucom-derived Penicillium sp.
- Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation
- Evaluation and enzyme-aided enhancement of anti-photoaging properties of Camellia japonica in UVA-irradiated keratinocytes
- Electrochemical quantification of biomarker myeloperoxidase
- Scopoletin: a review of its source, biosynthesis, methods of extraction, and pharmacological activities
- Occurrence of Z-2-oxo-4-methyl-3-pentene-1,5-dioic acid and its regioisomer 4-methylene-2-oxo-glutaric acid in tulip tissues
- Phytochemical analysis, antioxidant, cytotoxic, and antimicrobial activities of golden chamomile (Matricaria aurea (Loefl.) Schultz Bip)
- Synthesis and characterization of silver nanoparticles using curcumin: cytotoxic, apoptotic, and necrotic effects on various cell lines
- Review Article
- A comparative analysis on the safety and efficacy of Covaxin versus other vaccines against COVID-19: a review
- Corrigendum
- Corrigendum to: an update on the progress of microbial biotransformation of commercial monoterpenes
Articles in the same Issue
- Frontmatter
- Research Articles
- In vitro anticancer and antibacterial potentials of selected medicinal plants and isolation and characterization of a natural compound from Withania coagulans
- New compounds from Sarcophyton glaucom-derived Penicillium sp.
- Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation
- Evaluation and enzyme-aided enhancement of anti-photoaging properties of Camellia japonica in UVA-irradiated keratinocytes
- Electrochemical quantification of biomarker myeloperoxidase
- Scopoletin: a review of its source, biosynthesis, methods of extraction, and pharmacological activities
- Occurrence of Z-2-oxo-4-methyl-3-pentene-1,5-dioic acid and its regioisomer 4-methylene-2-oxo-glutaric acid in tulip tissues
- Phytochemical analysis, antioxidant, cytotoxic, and antimicrobial activities of golden chamomile (Matricaria aurea (Loefl.) Schultz Bip)
- Synthesis and characterization of silver nanoparticles using curcumin: cytotoxic, apoptotic, and necrotic effects on various cell lines
- Review Article
- A comparative analysis on the safety and efficacy of Covaxin versus other vaccines against COVID-19: a review
- Corrigendum
- Corrigendum to: an update on the progress of microbial biotransformation of commercial monoterpenes
