Kumarin ve izokumarin türevlerinin anti-enflamatuar aktivite profillerinin araştırılması

Öz

Kumarinler (2H-1-benzopiran-2-on) ve izokumarinler (1H-2-benzopiran-1-on), çoğunlukla bitkilerde ve mikroorganizmalarda bulunan doğal olarak oluşan biyolojik aktif bileşiklerdir. Çok sayıda kumarin ve izokumarin türevi, farklı mekanizmalar yoluyla hafif ila çok güçlü antienflamatuar aktiviteye sahip olacak şekilde tasarlanmış, sentezlenmiş ve değerlendirilmiştir. Çok sayıda araştırma raporu, kumarin ve izokumarin ana yapısını, antienflamatuar ilaçların geliştirilmesi için potansiyel adaylar olarak göstermiştir. Bu doğal ürünlerin yapısal çeşitliliği ve biyolojik aktivitesi ile ilgili mevcut literatür gözden geçirilmiştir. Bu derleme makalesinde; çeşitli çalışmalar sonucu elde edilen antienflamatuar aktiviteye sahip doğal ve sentetik kumarin ve izokumarin türevlerinin karşılaştırmalı analizi gerçekleştirilmiş ve etkili antienflamatuar ilaçların tasarımında yol gösterici olması amacıyla kumarin ve izokumarin ana yapısı etrafında genel bir yapı-aktivite ilişkisi oluşturulmuştur.

Anahtar Kelimeler

• Kumarin
• izokumarin
• enflamasyon
• antienflamatuar

Investigation of anti-Inflammatory activity profiles of coumarin and isocoumarine derivatives

Öz

Coumarins (2H-1-benzopyran-2-one) and isocumarins (1H-2-benzopyran-1-one) are naturally occurring biologically active compounds mostly found in plants as well as microorganisms. A large number of coumarin and isocoumarin derivatives have been designed, synthesized, and evaluated to have mild-to-very potent anti-inflammatory activity through different mechanisms. Numerous research reports have indicated the coumarin and isocoumarin nucleus as potential candidates for the development of anti-inflammatory drugs. The available literature on the structural diversity and biological activity of these natural products has been reviewed. In this review article; Comparative analysis of natural and synthetic coumarin and isocoumarin derivatives with anti-inflammatory activity obtained as a result of various studies was carried out and a general structure-activity relationship was established around the main structure of coumarin and isocoumarin to guide the design of effective anti-inflammatory drugs.

Anahtar Kelimeler

• Coumarin
• isocoumarin
• inflammation
• anti-inflammatory

Kaynakça

1. [1] Barry, R. D. “Isocoumarins. Developments Since 1950,” Chemical Reviews, (2002), 64, 3, 229–260, doi: 10.1021/cr60229a002.
2. [2] Borges, F., Roleira, F., Milhazes, N., Santana, L., and Uriarte, E. “Simple Coumarins and Analogues in Medicinal Chemistry: Occurrence, Synthesis and Biological Activity,” Current Medicinal Chemistry, (2005), 12, 8, 887–916, doi: 10.2174/0929867053507315.
3. [3] Matos, M. J., Santana, L., Uriarte, E., Abreu, O. A., Molina, E., and Yordi, E. G. “Coumarins — An Important Class of Phytochemicals,” Phytochemicals - Isolation, Characterisation and Role in Human Health, (2015), 1-30, doi: 10.5772/59982.
4. [4] Stefanachi, A., Leonetti, F., Pisani, L., Catto M.,, and Carotti, A. "Coumarin: A natural, privileged and versatile scaffold for bioactive compounds", Molecules, (2018), 23(2), 250, 1-34, DOI: 10.3390/molecules23020250
5. [5] Kumar, K. A., Nagamallu, R., and Govindappa, V. K., “Comprehensive review on coumarins : Molecules of potential chemical and pharmacological interest,” Journal of Chemical and Pharmaceutical Research, (2015), 7, 9, 67–81,
6. [6] Fylaktakidou, K., Hadjipavlou-Litina, D., Litinas, K., and Nicolaides, D. “Natural and Synthetic Coumarin Derivatives with Anti-Inflammatory / Antioxidant Activities,” Current Pharmaceutical Design, (2005), 10, 30, 3813–3833, doi: 10.2174/1381612043382710.
7. [7] Shabir, G., Saeed, A., and El-Seedi, H. R. “Natural isocoumarins: Structural styles and biological activities, the revelations carry on …,” Phytochemistry, (2020), 181, 112568, doi: 10.1016/j.phytochem.112568.
8. [8] Saeed, A. “Isocoumarins, miraculous natural products blessed with diverse pharmacological activities,” European Journal of Medicinal Chemistry, (2016), 116, 290–317, doi: 10.1016/j.ejmech.2016.03.025.

9. [9] Medzhitov, R. “Origin and physiological roles of inflammation,” Nature, (2008), 454, 7203, 428–435, doi: 10.1038/nature07201.
10. [10] Nathan, C. “Points of control in inflammation,” Nature, (2002) 420, 6917, 846–852.
11. [11] Dhingra, A., Chopra, B., Dass, R,. Mittal, S. “An update on Anti-inflammatory Compounds: A Review,” Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, (2015), 14, 2, 81–97, doi: 10.2174/1871523014666150514102027.
12. [12] Perez, R. M. “Anti-Inflammatory Activity of Compounds Isolated from Plants,” The Scientific World Journal, (2001), 1, 713–784, doi: 10.1100/tsw.2001.77.
13. [13] Garg, S. S., Gupta, J., Sharma, S., and Sahu, D. “An insight into the therapeutic applications of coumarin compounds and their mechanisms of action,” European Journal of Pharmaceutical Sciences, (2020), 152, 105424, doi: 10.1016/j.ejps.2020.105424.
14. [14] Sethna, N. M., Shah, S. M. “The Chemistry of Coumarins,” Chemical Reviews, (1945), 36, 1, 1–62, doi.org/10.1021/cr60113a001
15. [15] Jain P. K., and Joshi, H., “Coumarin: Chemical and pharmacological profile,” Journal of Applied Pharmaceutical Science, (2012), 2, 6, 236–240, doi: 10.7324/JAPS.2012.2643.
16. [16] Dighe, N., Pattan, S. R., Dengale, S. S., Musmade, S., Deepak, Madhuri, S., Tambe, V., and Hole, M. B. “Synthetic and pharmacological profiles of coumarins: A review,” Archives of Applied Science Research, (2010), 2, 65–71, http://scholarsresearchlibrary.com/aasr-vol2-iss2/AASR-2010-2-2-65-71.pdf.
17. [17] Kulkarni, C. M., Kulkarni, M. V., Lin, G. M., Sun, C. H. “Recent advances in coumarins and 1-azacoumarins as versatile biodynamic agents,” Current Medicinal Chemistry, (2006), 13, 23, 2795–2818, doi:0.2174/092986706778521968.
18. [18] Bansal, Y., Sethi, P., and Bansal, G. “Coumarin: A potential nucleus for anti-inflammatory molecules,” Medicinal Chemistry Research, (2013), 22, 7, 3049–3060, doi: 10.1007/s00044-012-0321-6.
19. [19] Piller, N. B. “A comparison of the effectiveness of some anti inflammatory drugs on thermal oedema,” British Journal of Experimental Pathology, (1975), 56, 6, 554–560.
20. [20] Witaicenis A., Seito, L. N., Chagas, A. da S., Luiz Jr, D. de Al., Luchini, A. C., Rodrigues-Orsi, P., Cestari, S. H., Stasi, L. C. Di. “Antioxidant and intestinal anti-inflammatory effects of plant-derived coumarin derivatives,” Phytomedicine : International Journal of Phytotherapy and Phytopharmacology Specifications, (2014), 21, 240–246.
21. [21] Casley-Smith JR, C.-S. J. “Modern treatment of lymphoedema II. The benzopyrones,” Australasian Journal of Dermatology, (1992), 33, 69–74.
22. [22] Maddi, V., Raghu, K. S., and Rao, M. N. A. “Synthesis and anti‐inflammatory activity of 3‐(benzylideneamino)coumarins in rodents,” Journal of Pharmaceutical Sciences, (1992), 81, 9,. 964–966, doi:10.1002/jps.2600810926.
23. [23] Gacche, R. N., Gond, D. S., Dhole, N. A., and Dawane, B. S., “Coumarin Schiff-bases: As antioxidant and possibly anti-inflammatory agents,” Journal of Enzyme Inhibition and Medicinal Chemistry,(2006), 21, 2, 157–161, doi: 10.1080/14756360500532671.
24. [24] Timonen, J. M., et al., “Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives,” European Journal of Medicinal Chemistry, (2011), 46, 9, 3845–3850, doi:10.1016/j.ejmech.2011.05.052.
25. [25] Sashidhara, K. V., et al., “Synthesis and anti-inflammatory activity of novel biscoumarin-chalcone hybrids,” Bioorganic Medicinal Chemistry Letters, (2011), 21, 15, 4480–4484, doi:10.1016/j.bmcl.2011.06.002.
26. [26] Srivastava, P., Vyas, V. K., Variya, B., Patel, P., Qureshi, G., and Ghate, M., “Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives,” Bioorganic Chemistry, (2016), 67, 130–138, doi: 10.1016/j.bioorg.2016.06.004.
27. [27] Abdellatif, A., Abdelall, A., Fadaly, W. A., and Kamel, G. M. “Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,3,5-triarylpyrazoline and 1,5-diarylpyrazole derivatives as selective COX-2 inhibitors,” Bioorganic Medicinal Chemistry Letters, (2016), 26, 2, 406–412, doi: 10.1016/j.bmcl.2015.11.105.
28. [28] Chen L. Z., et al. “New arylpyrazoline-coumarins: Synthesis and anti-inflammatory activity,” European Journal of Medicinal Chemistry, (2017), 138, 170–181, doi: 10.1016/j.ejmech.2017.06.044.
29. [29] Fattah, T. A., et al. “Functionalized furo[3,2-c]coumarins as anti-proliferative, anti-lipolytic, and anti-inflammatory compounds: Synthesis and molecular docking studies,” Journal of Molecular Structure, (2019), 1179, 390–400, doi: 10.1016/j.molstruc.2018.11.014.
30. [30] Deng, D., et al. “Synthesis and discovery of new compounds bearing coumarin scaffold for the treatment of pulmonary fibrosis,” European Journal of Medicinal Chemistry, (2019), 111790, doi: 10.1016/j.ejmech.2019.111790.
31. [31] Tapanyiğit, O., Demirkol, O., Güler, E., Erşatır, M., Çam, M. E., and Giray, E. S., “Synthesis and investigation of anti-inflammatory and anticonvulsant activities of novel coumarin-diacylated hydrazide derivatives,” Arabian Journal of Chemistry, (2020), 13, 12, 9105–9117 , doi: 10.1016/j.arabjc.2020.10.034.
32. [32] Naik, N. S., et al. “Synthesis of novel aryl and coumarin substituted pyrazolo[1,5-a]pyrimidine derivatives as potent anti-inflammatory and anticancer agents,” Chemical Data Collections, (2020), 30, 100550, doi: 10.1016/j.cdc.2020.100550.
33. [33] Muthanna, M. H. A., Farhan, S. “Synthesis, Characterization and Anti-Inflammatory Study of New Heterocyclic Coumarin Derivatives,” Indian Journal of Forensic Medicine & Toxicology, (2021), 15, 1, 2363–2369.
34. [34] Kontogiorgis, C. A., and Hadjipavlou-Litina, D. J. “Synthesis and antiinflammatory activity of coumarin derivatives,” Journal of Medicinal Chemistry, (2005), 48, 20, 6400–6408, doi: 10.1021/jm0580149.
35. [35] Buran, B. K., Reis, R., Sipahi, H., “Piperazine and piperidine‐substituted 7‐hydroxy coumarins for the development of anti‐inflammatory agents,” Archiv der Pharmazie (Weinheim)., (2021), 1–11, doi: https://doi.org/10.1002/ardp.202000354.
36. [36] Kang, Y. S., Chung, Y. C., Lee, J. N., Kim, B. S., Hyun, C.-G. “Anti-Inflammatory Effects of 6,7-Dihydroxy-4-Methylcoumarin on LPS-Stimulated Macrophage Phosphorylation in MAPK Signaling Pathways,” Natural product communications, (2021), 16, 5.
37. [37] Pal, S., Chatare, V., and Pal, M. “Isocoumarin and Its Derivatives: An Overview on their Synthesis and Applications,” Current Organic Chemistry, (2011), 15, 5, 782–800, doi: 10.2174/138527211794518970.
38. [38] Napolitano, E. “Synthesis of isocoumarins over the last decade: a review,” Organic Preparations and Procedures International, (1997), 29, 631–664, doi: DOI: 10.1080/00304949709355245.
39. [39] Braca, A., Bader, A., and Tommasi, N. D., “Plant and fungi 3,4-dihydroisocoumarins: Structures, biological activity, and taxonomic relationships” Studies in Natural Products Chemistry, (2012), 37, 191–215. doi:10.1016/B978-0-444-59514-0.00007-9.
40. [40] Saikia P., and Gogoi, S. “Isocoumarins: General Aspects and Recent Advances in their Synthesis,” Advanced Synthesis and Catalysis, (2018), 360, 11, 2063–2075, doi: 10.1002/adsc.201800019.
41. [41] Saddiqa, A., Usman, M., and Çakmak, O. “Isocoumarins and 3,4-dihydroisocoumarins, amazing natural products: A review,” Turkish Journal of Chemistry, (2017), 41, 2, 153–178, doi: 10.3906/kim-1604-66.
42. [42] Tianpanich, P. K. K., Prachya, S., Wiyakrutta, S., Mahidol, C., Ruchirawat, S., “Radical scavenging and antioxidant activities of isocoumarins and a phthalide from the endophytic fungus Colletotrichum sp.,” Journal of Natural Products, (2010), 74, 1, 79–81.
43. [43] Di Stasi, J. G. L.C., Camuesco, D., Nieto, A., Vilegas, W., Zarzuelo, A. “Intestinal anti-inflammatory activity of paepalantine, an isocoumarin isolated from the capitula of Paepalanthus bromelioides, in the trinitrobenzenesulphonic acid model of rat colitis,” Plantamedica, (2004), 70, 4, 293–305.
44. [44] Powers, J. C., and Kam, C. M. “Isocoumarin inhibitors of serine peptidases,” Methods in Enzymology, (1994), 244, 442–457, doi: 10.1016/0076-6879(94)44033-6.
45. [45] Odake, J. C. P. S., Kam, C.M., Narasimhan, L., Poe, M., Blake, J.T., Krahenbuhl, O., Tschopp, J., “Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins,” Biochemistry, (1991), 30, 2217–2225.
46. [46] Kerrigan, J. E., Oleksyszyn, J., Kam, C.-M., Selzler, J. and Powers, J. C. “Mechanism-Based Isocoumarin Inhibitors for Human Leukocyte Elastase. Effect of the 7-Amino Substituent and 3-Alkoxy Group in 3-Alkoxy-7-amino-4-chloroisocoumarins on Inhibitory Potency,” Journal of Medicinal Chemistry, (2002), 38, 3,. 544–552, doi: 10.1021/jm00003a017.
47. [47] Wade Harper, J., and Powers, J. C., “Reaction of serine proteases with substituted 3-alkoxy-4-chloroisocoumarins and 3-alkoxy-7-amino-4-chloroisocoumarins: new reactive mechanism-based inhibitors,” Biochemistry, (2002), 24, 25, 7200–7213, doi: 10.1021/bi00346a028.
48. [48] Zimmerman, M., Morman, H., Mulvey, D., Jones, H., Frankshun, R., and Ashe, B. M., “Inhibition of elastase and other serine proteases by heterocyclic acylating agents,” Journal of Biological Chemistry, (1980), 255, 20, 9848–9851, doi: 10.1016/s0021-9258(18)43470-9.
49. [49] Qadeer, G., Rama, N. H., and Garduño-Ramírez, M. L. “Synthesis and anti-inflammatory activity of fluorinated isocoumarins and 3,4-dihydroisocoumarins,” Journal of Fluorine Chemistry, (2007), 128, 6, 641–646, doi: 10.1016/j.jfluchem.2007.02.021.
50. [50] Hui, D. Y., “Molecular biology of enzymes involved with cholesterol ester hydrolysis in mammalian tissues,” Biochimica et Biophysica Acta - Lipids and Lipid Metabolism, (1996), 1303, 1. Elsevier B.V., 1–14, doi: 10.1016/0005-2760(96)00085-9.
51. [51] Howles, P. N., Carter, C. P., and Hui, D. Y., “Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice,” Journal of Biological Chemistry, (1996), 271, 12, 7196–7202, doi: 10.1074/jbc.271.12.7196.
52. [52] Heynekamp, J. J., Hunsaker, L. A., Vander Jagt, T. A., Royer, R. E., Deck, L. M., and Vander Jagt, D. L., “Isocoumarin-based inhibitors of pancreatic cholesterol esterase,” Bioorganic Medicinal Chemistry, (2008), 16, 9, 5285–5294, doi: 10.1016/j.bmc.2008.03.016.
53. [53] Ramanan, M., Sinha, S., Sudarshan, K., Aidhen, I. S., and Doble, M. “Inhibition of the enzymes in the leukotriene and prostaglandin pathways in inflammation by 3-aryl isocoumarins,” European Journal of Medicinal Chemistry, (2016), 124, 428–434, doi: 10.1016/j.ejmech.2016.08.066.
54. [54] Zhang, Y., et al., “Compound GDC, an Isocoumarin Glycoside, Protects against LPS-Induced Inflammation and Potential Mechanisms In Vitro,” Inflammation, (2019), 42, 2, 506–515, doi: 10.1007/s10753-018-0908-2.
55. [55] Thirupataiah, B., Reddy, G. S., Ghule, S. S., Kumar, J. S., Mounika, G., et el., “Synthesis of 11,12-dihydro benzo[c]phenanthridines via a Pd-catalyzed unusual construction of isocoumarin ring/FeCl3-mediated intramolecular arene-allyl cyclization: First identification of a benzo[c]phenanthridine based PDE4 inhibitor,” Bioorganic Chemistry, (2020), 97, doi: doi:10.1016/j.bioorg.2020.103691.
56. [56] Thirupataiaha, B., Mounika, G., Reddy, G. S., Kumar, J. S., Hossain. K. A., et al. “PdCl2-catalyzed synthesis of a new class of isocoumarin derivatives containing aminosulfonyl / aminocarboxamide moiety: First identification of a isocoumarin based PDE4 inhibitor,” European Journal of Medicinal Chemistry, (2021), 221, 0223–5234, doi: https://doi.org/10.1016/j.ejmech.2021.113514