Therapeutic Journey and Recent Advances in the Synthesis of Coumarin
Derivatives

Shweta       Sinha; Kuldeep       Singh; Akash       Ved; Syed    Misbahul    Hasan; Samar       Mujeeb
doi:10.2174/1389557521666211116120823
Abstract

Background: Coumarin is an oxygen-containing compound in medicinal chemistry. Coumarin plays an important role in both natural systems like plants and synthetic medicinal applications as drug molecules. Many structurally different coumarin compounds have been found to possess a wide range of similarities with the vital molecular targets in terms of their pharmacological action and small modifications in their structures, resulting in significant changes in their biological activities.
Objective: This review provides detailed information regarding the studies focused on the recent advances in various pharmacological aspects of coumarins.
Methods: Various oxygen-containing heterocyclic compounds represent remarkable biological significance. The fused aromatic oxygen-heterocyclic nucleus can change its electron density, thus altering the chemical, physical and biological properties, respectively, due to its multiple binding modes with the receptors, which play a crucial role in the pharmacological screening of drugs. Several heterocyclic compounds have been synthesized which have their nuclei derived from various plants and animals. In coumarins, the benzene ring is fused with a pyrone nucleus which provides stability to the nucleus. Coumarins have shown a wide range of pharmacological activities, such as anti-tumor, anticoagulant, anti-inflammatory, anti-oxidant, antiviral, antimalarial, anti-HIV, antimicrobial, etc.
Results: Reactive oxygen species, like superoxide anion, hydroxyl radical, and hydrogen peroxide, are a type of unstable molecule containing oxygen, which reacts with other molecules in the cell during metabolism; however, when the number of reactive oxygen species increases, it may lead to cytotoxicity, thereby damaging the biological macromolecules. Hydroxyl Radical (OH) is a strong oxidizing agent and it is responsible for the cytotoxicity caused by oxygen in different plants, animals, and other microbes. Coumarin is the oldest and effective compound having antimicrobial, anti-inflammatory, antioxidant, antidepressant, analgesic, anticonvulsant activities, etc. Naturally existing coumarin compounds act against SARS-CoV-2 by preventing viral replication and targeting the active site against the M^pro target protein.
Conclusion: This review highlights the different biological activities of coumarin derivatives. In this review, we provide an updated summary of the researches which are related to recent advances in biological activities of coumarins analogs and their most recent activities against COVID -19. Natural compounds act as a rich resource for novel drug development against various SARS-CoV-2 viral strains and viruses, like herpes simplex virus, influenza virus, human immunodeficiency virus, hepatitis B and C viruses, middle east respiratory syndrome, and severe acute respiratory syndrome.
Keywords: Coumarin, anticonvulsant activity, anticoagulant activity, antioxidant activity, anticancer, antimicrobial, SARS-CoV-2.
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[1] 
Hassan, M.Z.; Osman, H.; Ali, M.A.; Ahsan, M.J.J. Therapeutic potential of coumarins as antiviral agents. Eur. J. Med. Chem.,  2016, 123, 236-255.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.056] [PMID: 27484512] 
[2] 
Venugopala, K.N.; Rashmi, V.; Odhav, B. Review on natural coumarin lead compounds for their pharmacological activity. BioMed Res. Int.,  2013, 2013, 963248.
[http://dx.doi.org/10.1155/2013/963248] [PMID: 23586066] 
[3] 
Kontogiorgis, C.A.; Savvoglou, K.; Hadjipavlou-Litina, D.J. Antiinflammatory and antioxidant evaluation of novel coumarin derivatives. J. Enzyme Inhib. Med. Chem.,  2006, 21(1), 21-29.
[http://dx.doi.org/10.1080/14756360500323022] [PMID: 16570501] 
[4] 
Najmanová, I.; Doseděl, M.; Hrdina, R.; Anzenbacher, P.; Filipský, T.; Říha, M.; Mladěnka, P. Cardiovascular effects of coumarins besides their antioxidant activity. Curr. Top. Med. Chem.,  2015, 15(9), 830-849.
[http://dx.doi.org/10.2174/1568026615666150220112437] [PMID: 25697565] 
[5] 
Skalicka-Wozniak, K.; Budzynska, B.; Biala, G.; Boguszewska-Czubara, A. Boguszewska-Czubara. Scopolamine-induced memory impairment is alleviated by xanthotoxin: Role of acetylcholinesterase and oxidative stress processes. ACS Chem. Neurosci.,  2018, 9(5), 1184-1194.
[http://dx.doi.org/10.1021/acschemneuro.8b00011] [PMID: 29378112] 
[6] 
Rohini, K.; Srikumar, P.S. Therapeutic role of coumarins and coumarin-related compounds. J. Thermodyn. Catal.,  2014, 5, 130-133.
[http://dx.doi.org/10.4172/2157-7544.1000130] 
[7] 
Popp, D.; Plugge, C.M.; Kleinsteuber, S.; Harms, H.; Sträuber, H. Inhibitory effect of coumarin on syntrophic fatty acid-oxidizing and methanogen-IC cultures and biogas reactor microbiomes. Appl. Environ. Microbiol.,  2017, 83(13), 00438-17.
[http://dx.doi.org/10.1128/AEM.00438-17] [PMID: 28432098] 
[8] 
Bryda, J.; Zagaja, M.; Szewczyk, A.; Andres-Mach, M. Coumarins as potential supportive medication for the treatment of epilepsy. Acta Neurobiol. Exp. (Warsz.),  2019, 79(2), 126-132.
[http://dx.doi.org/10.21307/ane-2019-011] [PMID: 31342949] 
[9] 
Othman, L.; Sleiman, A.; Abdel-Massih, R.M. Antimicrobial activity of polyphenols and alkaloids in middle eastern plants. Front. Microbiol.,  2019, 10, 911.
[http://dx.doi.org/10.3389/fmicb.2019.00911] [PMID: 31156565] 
[10] 
Curir, P.; Galeotti, F.; Dolci, M.; Barile, E.; Lanzotti, V. Pavietin, a coumarin from Aesculus pavia with antifungal activity. J. Nat. Prod.,  2007, 70(10), 1668-1671.
[http://dx.doi.org/10.1021/np070295v] [PMID: 17914881] 
[11] 
Lee, K.H. Current developments in the discovery and design of new drug candidates from plant natural product leads. J. Nat. Prod.,  2004, 67(2), 273-283.
[http://dx.doi.org/10.1021/np030373o] [PMID: 14987069] 
[12] 
Xu, J.; Kjer, J.; Sendker, J.; Wray, V.; Guan, H.; Edrada, R.; Müller, W.E.G.; Bayer, M.; Lin, W.; Wu, J.; Proksch, P. Cytosporones, coumarins, and an alkaloid from the endophytic fungus Pestalotiopsis sp. isolated from the Chinese mangrove plant Rhizophora mucronata. Bioorg. Med. Chem.,  2009, 17(20), 7362-7367.
[http://dx.doi.org/10.1016/j.bmc.2009.08.031] [PMID: 19762244] 
[13] 
Fylaktakidou, K.C.; Hadjipavlou-Litina, D.J.; Litinas, K.E.; Nicolaides, D.N. Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities. Curr. Pharm. Des.,  2004, 10(30), 3813-3833.
[http://dx.doi.org/10.2174/1381612043382710] [PMID: 15579073] 
[14] 
Jung, J.C.; Park, O.S. Synthetic approaches and biological activities of 4-hydroxycoumarin derivatives. Molecules,  2009, 14, 4790-4803.
[http://dx.doi.org/10.3390/molecules14114790] 
[15] 
Musicki, B.; Periers, A.M.; Piombo, L.; Laurin, P.; Klich, M. Dupuis- Hamelin, C.; Lassaigne, P.; Bonnefoy, A. Noviose mimics of the coumarin inhibitors of gyrase B. Tetrahedron Lett.,  2003, 44, 9259-9262.
[http://dx.doi.org/10.1016/j.tetlet.2003.10.076] 
[16] 
Peng, H.; Marians, K.J. Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions. J. Biol. Chem.,  1993, 268(32), 24481-24490.
[http://dx.doi.org/10.1016/S0021-9258(20)80551-1] [PMID: 8227000] 
[17] 
Chimenti, F.; Secci, D.; Bolasco, A.; Chimenti, P.; Bizzarri, B.; Granese, A.; Carradori, S.; Yáñez, M.; Orallo, F.; Ortuso, F.; Alcaro, S. Synthesis, molecular modeling, and selective inhibitory activity against human monoamine oxidases of 3-carboxamido-7-substituted coumarins. J. Med. Chem.,  2009, 52(7), 1935-1942.
[http://dx.doi.org/10.1021/jm801496u] [PMID: 19267475] 
[18] 
Anand, P.; Singh, B.; Singh, N. A review on coumarins as acetylcholinesterase inhibitors for Alzheimer’s disease. Bioorg. Med. Chem.,  2012, 20(3), 1175-1180.
[http://dx.doi.org/10.1016/j.bmc.2011.12.042] [PMID: 22257528] 
[19] 
Noolvi, M.N.; Patel, H.M.; Kaur, T.A. QSAR analysis of coumarin derivatives as TNF-inhibitor-A rational approach to anticancer drug design. Lett. Drug Des. Discov.,  2011, 8, 868-876.
[http://dx.doi.org/10.2174/157018011797200768] 
[20] 
Beillerot, A.; Domínguez, J.C.R.; Kirsch, G.; Bagrel, D. Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin. Bioorg. Med. Chem. Lett.,  2008, 18(3), 1102-1105.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.004] [PMID: 18164200] 
[21] 
Orita, M.; Yamamoto, S.; Katayama, N.; Aoki, M.; Takayama, K.; Yamagiwa, Y.; Seki, N.; Suzuki, H.; Kurihara, H.; Sakashita, H.; Takeuchi, M.; Fujita, S.; Yamada, T.; Tanaka, A. Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: Discovery and X-ray crystallography. J. Med. Chem.,  2001, 44(4), 540-547.
[http://dx.doi.org/10.1021/jm000386o] [PMID: 11170644] 
[22] 
Chilin, A.; Battistutta, R.; Bortolato, A.; Cozza, G.; Zanatta, S.; Poletto, G.; Mazzorana, M.; Zagotto, G.; Uriarte, E.; Guiotto, A.; Pinna, L.A.; Meggio, F.; Moro, S. Coumarin as attractive casein kinase 2 (CK2) inhibitor scaffold: an integrate approach to elucidate the putative binding motif and explain structure-activity relationships. J. Med. Chem.,  2008, 51(4), 752-759.
[http://dx.doi.org/10.1021/jm070909t] [PMID: 18251491] 
[23] 
Kumar, S.; Singh, B.K.; Kalra, N.; Kumar, V.; Kumar, A.; Prasad, A.K.; Raj, H.G.; Parmar, V.S.; Ghosh, B. Novel thiocoumarins as inhibitors of TNF-alpha induced ICAM-1 expression on Human Umbilical Vein Endothelial Cells (HUVECs) and microsomal lipid peroxidation. Bioorg. Med. Chem.,  2005, 13(5), 1605-1613.
[http://dx.doi.org/10.1016/j.bmc.2004.12.013] [PMID: 15698778] 
[24] 
Reddy, P.V.K.; Kumar, P.N.; Chandramouli, G.V.P. Synthesis and antimicrobial activity of 6, 60-arylidene-bis-[5-hydroxy-9-methyl-2, 3-diaryl thieno[3, 2-g-]thiocoumarins J. Heterocycl. Chem.,  2005, 42, 283-286.
[http://dx.doi.org/10.1002/jhet.5570420216] 
[25] 
Barot, K.P.; Jain, S.V.; Kremer, L. Recent advances and therapeutic journey of coumarins: Current status and perspectives. Med. Chem. Res.,  2015, 24, 2771-2798.
[http://dx.doi.org/10.1007/s00044-015-1350-8] 
[26] 
Hadjipavlou-Litina, D.J.; Litinas, K.E.; Kontogiorgis, C. The anti-inflammatory effect of coumarin and its derivatives. Antiinflamm. Antiallergy Agents Med. Chem.,  2007, 6(4), 293-306.
[http://dx.doi.org/10.2174/187152307783219989] 
[27] 
Kim, Y.; Lee, J. Esculetin, a coumarin derivative, suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes. J. Funct. Foods,  2015, 12, 509-515.
[http://dx.doi.org/10.1016/j.jff.2014.12.004] 
[28] 
Hodák, K.; Jakesová, V.; Dadák, V. On the antibiotic effects of natural coumarins. VI. The relation of structure to the antibacterial effects of some natural coumarins and the neutralization of such effects. Cesk. Farm.,  1967, 16(2), 86-91.
[PMID: 6044315] 
[29] 
Schinkovitz, A.; Gibbons, S.; Stavri, M.; Cocksedge, M.J.; Bucar, F. Ostruthin: An antimycobacterial coumarin from the roots of Peucedanum ostruthium. Planta Med.,  2003, 69(4), 369-371.
[http://dx.doi.org/10.1055/s-2003-38876] [PMID: 12709907] 
[30] 
Burlison, J.A.; Neckers, L.; Smith, A.B.; Maxwell, A.; Blagg, B.S. Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90. J. Am. Chem. Soc.,  2006, 128(48), 15529-15536.
[http://dx.doi.org/10.1021/ja065793p] [PMID: 17132020] 
[31] 
Neu, H.C.; Chin, N.X.; Labthavikul, P. Antibacterial activity of coumermycin alone and in combination with other antibiotics. Antimicrob. Agents Chemother.,  1984, 25(6), 687-689.
[http://dx.doi.org/10.1128/AAC.25.6.687] [PMID: 6331295] 
[32] 
Xu, Z.; Jakobi, K.; Welzel, K.; Hertweck, C. Biosynthesis of the antitumor agent chartreusin involves the oxidative rearrangement of an anthracyclic polyketide. Chem. Biol.,  2005, 12(5), 579-588.
[http://dx.doi.org/10.1016/j.chembiol.2005.04.017] [PMID: 15911378] 
[33] 
Kontogiorgis, C.; Detsi, A.; Hadjipavlou-Litina, D. Coumarin-based drugs: A patent review (2008 -- present). Expert Opin. Ther. Pat.,  2012, 22(4), 437-454.
[http://dx.doi.org/10.1517/13543776.2012.678835] [PMID: 22475457] 
[34] 
Luo, K.W.; Sun, J.G.; Chan, J.Y.; Yang, L.; Wu, S.H.; Fung, K.P.; Liu, F.Y. Anticancer effects of imperatorin isolated from Angelica dahurica: Induction of apoptosis in HepG2 cells through both death-receptor- and mitochondria-mediated pathways. Chemotherapy,  2011, 57(6), 449-459.
[http://dx.doi.org/10.1159/000331641] [PMID: 22189406] 
[35] 
Yu, X.; Wen, Y.; Liang, C-G.; Liu, J.; Ding, Y-B.; Zhang, W-H. Design, synthesis and antifungal activity of psoralen derivatives. Molecules,  2017, 22(10), 1672.
[http://dx.doi.org/10.3390/molecules22101672] [PMID: 28991209] 
[36] 
Hussain, M.I.; Syed, Q.A.; Khattak, M.N.K. Natural product coumarins: Biological and pharmacological perspectives. Biologia.,  2019, 74, 863-888.
[http://dx.doi.org/10.2478/s11756-019-00242-x] 
[37] 
Palacharla, R.C.; Molgara, P.; Panthangi, H.R.; Boggavarapu, R.K.; Manoharan, A.K.; Ponnamaneni, R.K.; Ajjala, D.R.; Nirogi, R. Methoxsalen as an in vitro phenotyping tool in comparison with 1-aminobenzotriazole. Xenobiotica,  2019, 49(2), 169-176.
[http://dx.doi.org/10.1080/00498254.2018.1434913] [PMID: 29382249] 
[38] 
Savaş, E.; Tavşanlı, H.; Catalkaya, G.; Capanoglu, E.; Tamer, C. The antimicrobial and antioxidant properties of garagurt: Traditional Cornelian cherry (Cornus mas) marmalade. Qual. Assur. Saf. Crops Foods,  2020, 12, 12-23.
[http://dx.doi.org/10.15586/qas.v12i2.627] 
[39] 
Tkachenko, H.; Buyun, L.; Terech-Majewska, E.; Osadowski, Z.; Sosnovsky, E.; Honcharenko, V.; Prokopiv, A. In vitro antibacterial efficacy of various ethanolic extracts obtained from Ficus spp. leaves against fish pathogen, Pseudomonas fluorescens. Arch. Pol. Fisheries,  2016, 2019(27), 15-26.
[40] 
Chiang, C-C.; Cheng, M-J.; Peng, C-F.; Huang, H-Y.; Chen, I.S. A novel dimeric coumarin analog and antimycobacterial constituents from Fatoua pilosa. Chem. Biodivers.,  2010, 7(7), 1728-1736.
[http://dx.doi.org/10.1002/cbdv.200900326] [PMID: 20658660] 
[41] 
Basile, A.; Sorbo, S.; Spadaro, V.; Bruno, M.; Maggio, A.; Faraone, N.; Rosselli, S. Antimicrobial and antioxidant activities of coumarins from the roots of Ferulago campestris (Apiaceae). Molecules,  2009, 14(3), 939-952.
[http://dx.doi.org/10.3390/molecules14030939] [PMID: 19255552] 
[42] 
Borges, F.; Roleira, F.; Milhazes, N.; Santana, L.; Uriarte, E. Simple coumarins and analogues in medicinal chemistry: Occurrence, synthesis and biological activity. Curr. Med. Chem.,  2005, 12(8), 887-916.
[http://dx.doi.org/10.2174/0929867053507315] [PMID: 15853704] 
[43] 
Foroozesh, M.; Sridhar, J.; Goyal, N.; Liu, J. Coumarins and P450s, studies reported to-date. Molecules,  2019, 24(8), 1620.
[http://dx.doi.org/10.3390/molecules24081620] [PMID: 31022888] 
[44] 
Lewis, D.F.V.; Ito, Y.; Lake, B.G. Metabolism of coumarin by human P450s: a molecular modelling study. Toxicol. In Vitro,  2006, 20(2), 256-264.
[http://dx.doi.org/10.1016/j.tiv.2005.08.001] [PMID: 16157466] 
[45] 
Jayashree, B.S.; Anuradha, D.; Venugopala, K.N. Synthesis and characterization of schiff bases of 2′-amino-4′-(6-chloro-3- coumarinyl)-thiazole as potential NSAIDs. Asian J. Chem.,  2005, 17, 2093-2097.
[46] 
Al-Majedy Yasameen, K.; Abdul Amir, H. Kadhum, Ahmed A.; Al-Amiery.; and Abu Bakar Mohamad. Coumarins: the antimicrobial agents. Syst. Rev. Pharm.,  2017, 8, 62.
[47] 
Behrami, A.; Krasniqi, I. Antibacterial activity of coumarine derivatives synthesized from 8- amino4,7-dihydroxy-chromen-2-one and comparison with standard drug. J. Chem. Pharm.,  2012, 4, 2495-2500.
[48] 
Khameneh, B.; Iranshahy, M.; Soheili, V.; Fazly Bazzaz, B.S. Review on plant antimicrobials: a mechanistic viewpoint. Antimicrob. Resist. Infect. Control,  2019, 8, 118.
[http://dx.doi.org/10.1186/s13756-019-0559-6] [PMID: 31346459] 
[49] 
Xu, X.T.; Deng, X.Y.; Chen, J.; Liang, Q.M.; Zhang, K.; Li, D.L.; Wu, P.P.; Zheng, X.; Zhou, R.P.; Jiang, Z.Y.; Ma, A.J.; Chen, W.H.; Wang, S.H. Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors. Eur. J. Med. Chem.,  2020, 189, 112013.
[http://dx.doi.org/10.1016/j.ejmech.2019.112013] [PMID: 31972390] 
[50] 
Reddy, N.S.; Gumireddy, K.; Mallireddigari, M.R.; Cosenza, S.C.; Venkatapuram, P.; Bell, S.C.; Reddy, E.P.; Reddy, M.V. Novel coumarin-3-(N-aryl)carboxamides arrest breast cancer cell growth by inhibiting ErbB-2 and ERK1. Bioorg. Med. Chem.,  2005, 13(9), 3141-3147.
[http://dx.doi.org/10.1016/j.bmc.2005.02.051] [PMID: 15809149] 
[51] 
Mohamed, T.K.; Batran, R.Z.; Elseginy, S.A.; Ali, M.M.; Mahmoud, A.E. Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis. Bioorg. Chem.,  2019, 85, 253-273.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.040] [PMID: 30641320] 
[52] 
Kontogiorgis, C.A.; Savvoglou, K.; Hadjipavlou, L.D.J. Evaluation of natural substances from Evolvulusalsinoides L. with the purpose of determining their antioxidant potency. J. Enzyme Inhib. Med. Chem.,  2006, 21, 21-29.
[http://dx.doi.org/10.1080/14756360500323022] [PMID: 16570501] 
[53] 
Kontogiorgis, C.; Hadjipavlou-Litina, D. Biological evaluation of several coumarin derivatives designed as possible anti-inflammatory/antioxidant agents. J. Enzyme Inhib. Med. Chem.,  2003, 18(1), 63-69.
[http://dx.doi.org/10.1080/1475636031000069291] [PMID: 12751823] 
[54] 
Fylaktakidou, K.C.; Gautam, D.; Hadjipavlou-Litina, D.; Kontogiorgis, C.; Litinas, K.; Nicolaides, D. Reactions of 4- methylchromene-2,7,8-trionewith phosphonium ylides. Synthesis and evaluation of fused 1,3-dioxolaneocoumarins as antioxidants and antiinflammatories. J. Chem. Soc. Perkin. Trans,  2001, 1, 3073-3079.
[http://dx.doi.org/10.1039/b103092m] 
[55] 
Nicolaides, D.; Gautam, D.; Litinas, K.; Hadjipavlou-Litina, D.; Kontogiorgis, C. Synthesis and biological evaluation of Benzo[7,8]chromeno[5,6-b][1,4]oxazin-3-ones. J. Heterocycl. Chem.,  2004, 41, 605-611.
[http://dx.doi.org/10.1002/jhet.5570410421] 
[56] 
Kayal, G.; Jain, K.; Malviya, S. Kharia. A: Comparative SAR of synthetic coumarin derivatives for their anti-inflammatory activity. Int. J. Pharm. Sci. Res.,  2014, 5, 3577-3583.
[57] 
Kalkhambkar, R.G.; Kulkarni, G.M.; Kamanavalli, C.M.; Premkumar, N.; Asdaq, S.M.B.; Sun, C.M. Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins. Eur. J. Med. Chem.,  2008, 43(10), 2178-2188.
[http://dx.doi.org/10.1016/j.ejmech.2007.08.007] [PMID: 17959273] 
[58] 
Hu, X-L.; Gao, C.; Xu, Z.; Liu, M.L.; Feng, L.S.; Zhang, G-D. Recent development of coumarin derivatives as potential antiplasmodial and antimalarial agents. Curr. Top. Med. Chem.,  2018, 18(2), 114-123.
[http://dx.doi.org/10.2174/1568026618666171215101158] [PMID: 29243579] 
[59] 
Pingaew, R.; Saekee, A.; Mandi, P.; Nantasenamat, C.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents. Eur. J. Med. Chem.,  2014, 85, 65-76.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.087] [PMID: 25078311] 
[60] 
Arshad, M.F.; Siddiqui, N.; Elkerdasy, A.; Al Rohaimi, A.H.; Khan, S.A. Anticonvulsant and neurotoxicity evaluation of some newly synthesized thiazolyl coumarin derivatives. Am. J. Pharmacol. Toxicol.,  2014, 9, 132.
[http://dx.doi.org/10.3844/ajptsp.2014.132.138] 
[61] 
Luszczki, J.J.; Wojda, E.; Andres-Mach, M.; Cisowski, W.; Glensk, M.; Glowniak, K.; Czuczwar, S.J. Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: A comparative study. Epilepsy Res.,  2009, 85(2-3), 293-299.
[http://dx.doi.org/10.1016/j.eplepsyres.2009.03.027] [PMID: 19406619] 
[62] 
Lee, S.; Sivakumar, K.; Shin, W.S.; Xie, F.; Wang, Q. Synthesis and anti-angiogenesis activity of coumarin derivatives. Bioorg. Med. Chem. Lett.,  2006, 16(17), 4596-4599.
[http://dx.doi.org/10.1016/j.bmcl.2006.06.007] [PMID: 16793260] 
[63] 
Sharma, A.; Gupta, Monika Synthesis and biological evaluation of coumarin as derivative antiproliferatives agents J. Chem. Pharm. Res.,  2018, 10, 120-132.
[64] 
Dwivedi, A.P.; Kumar, S.; Varshney, V.; Singh, A.B.; Srivastava, A.K.; Sahu, D.P. Synthesis and antihyperglycemic activity of novel N-acyl-2-arylethylamines and N-acyl-3-coumarylamines. Bioorg. Med. Chem. Lett.,  2008, 18(7), 2301-2305.
[http://dx.doi.org/10.1016/j.bmcl.2008.03.003] [PMID: 18353644] 
[65] 
Yeni, P.G.; Hammer, S.M.; Carpenter, C.C.; Cooper, D.A.; Fischl, M.A.; Gatell, J.M.; Gazzard, B.G.; Hirsch, M.S.; Jacobsen, D.M.; Katzenstein, D.A.; Montaner, J.S.; Richman, D.D.; Saag, M.S.; Schechter, M.; Schooley, R.T.; Thompson, M.A.; Vella, S.; Volberding, P.A. Antiretroviral treatment for adult HIV infection in 2002: Updated recommendations of the International AIDS Society-USA Panel. JAMA,  2002, 288(2), 222-235.
[http://dx.doi.org/10.1001/jama.288.2.222] [PMID: 12095387] 
[66] 
Márquez, N.; Sancho, R.; Bedoya, L.M.; Alcamí, J.; López-Pérez, J.L.; Feliciano, A.S.; Fiebich, B.L.; Muñoz, E. Mesuol, a natural occurring 4-phenylcoumarin, inhibits HIV-1 replication by targeting the NF-kappaB pathway. Antiviral Res.,  2005, 66(2-3), 137-145.
[http://dx.doi.org/10.1016/j.antiviral.2005.02.006] [PMID: 15911030] 
[67] 
Yu, D.; Suzuki, M.; Xie, L.; Morris-Natschke, S.L.; Lee, K.H. Recent progress in the development of coumarin derivatives as potent anti-HIV agents. Med. Res. Rev.,  2003, 23(3), 322-345.
[http://dx.doi.org/10.1002/med.10034] [PMID: 12647313] 
[68] 
Kirkiacharian, S.; Thuy, D.T.; Sicsic, S.; Bakhchinian, R.; Kurkjian, R.; Tonnaire, T. Structure-activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1 protease inhibitors. Farmaco,  2002, 57(9), 703-708.
[http://dx.doi.org/10.1016/S0014-827X(02)01264-8] [PMID: 12385519] 
[69] 
Lyndem, S.; Sarmah, S.; Das, S. Singha, Roy. A. In silico screening of naturally occurring coumarin derivatives for the inhibition of the main protease of SARS-CoV-2 ChemRxiv, 2020.
[70] 
Chen, F.E.; Huang, J. Reserpine: A challenge for total synthesis of natural products. Chem. Rev.,  2005, 105(12), 4671-4706.
[http://dx.doi.org/10.1021/cr050521a] [PMID: 16351058] 
[71] 
Wu, C.Y.; Jan, J.T.; Ma, S.H.; Kuo, C.J.; Juan, H.F.; Cheng, Y.S.; Hsu, H.H.; Huang, H.C.; Wu, D.; Brik, A.; Liang, F.S.; Liu, R.S.; Fang, J.M.; Chen, S.T.; Liang, P.H.; Wong, C.H. Small molecules targeting severe acute respiratory syndrome human coronavirus. Proc. Natl. Acad. Sci. USA,  2004, 101(27), 10012-10017.
[http://dx.doi.org/10.1073/pnas.0403596101] [PMID: 15226499] 
[72] 
Yang, Q.Y.; Tian, X.Y.; Fang, W.S. Bioactive coumarins from Boenninghausenia sessilicarpa. J. Asian Nat. Prod. Res.,  2007, 9(1), 59-65.
[http://dx.doi.org/10.1080/10286020500382397] [PMID: 17365191] 
[73] 
Li, S.Y.; Chen, C.; Zhang, H.Q.; Guo, H.Y.; Wang, H.; Wang, L.; Zhang, X.; Hua, S.N.; Yu, J.; Xiao, P.G.; Li, R.S.; Tan, X. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res.,  2005, 67(1), 18-23.
[http://dx.doi.org/10.1016/j.antiviral.2005.02.007] [PMID: 15885816] 
[74] 
Kim, J.Y.; Kim, Y.I.; Park, S.J.; Kim, I.K.; Choi, Y.K.; Kim, S.H. Safe, high-throughput screening of natural compounds of MERS-CoV entry inhibitors using a pseudovirus expressing MERS-CoV spike protein. Int. J. Antimicrob. Agents,  2018, 52(5), 730-732.
[http://dx.doi.org/10.1016/j.ijantimicag.2018.05.003] [PMID: 29772395] 
[75] 
Cheng, P.W.; Ng, L.T.; Chiang, L.C.; Lin, C.C. Antiviral effects of saikosaponins on human coronavirus 229E in vitro. Clin. Exp. Pharmacol. Physiol.,  2006, 33(7), 612-616.
[http://dx.doi.org/10.1111/j.1440-1681.2006.04415.x] [PMID: 16789928] 
[76] 
Kim, D.E.; Min, J.S.; Jang, M.S.; Lee, J.Y.; Shin, Y.S.; Song, J.H.; Kim, H.R.; Kim, S.; Jin, Y.H.; Kwon, S. Natural bis-benzylisoquinoline alkaloids-tetrandrine, fangchinoline, and cepharanthine, inhibit human coronavirus OC43 infection of MRC-5 human lung cells. Biomolecules,  2019, 9(11), 696.
[http://dx.doi.org/10.3390/biom9110696] [PMID: 31690059] 
[77] 
Jeong, C.S.; Hyun, J.E.; Kim, Y.S. Ginsenoside Rb1: The anti-ulcer constituent from the head of Panax ginseng. Arch. Pharm. Res.,  2003, 26(11), 906-911.
[http://dx.doi.org/10.1007/BF02980198] [PMID: 14661855] 
[78] 
Xian, Y.; Zhang, J.; Bian, Z.; Zhou, H.; Zhang, Z.; Lin, Z.; Xu, H. Bioactive natural compounds against human coronaviruses: A review and perspective. Acta Pharm. Sin. B,  2020, 10(7), 1163-1174.
[http://dx.doi.org/10.1016/j.apsb.2020.06.002] [PMID: 32834947] 
[79] 
Tortorici, M.A.; Walls, A.C.; Lang, Y.; Wang, C.; Li, Z.; Koerhuis, D.; Boons, G.J.; Bosch, B.J.; Rey, F.A.; de Groot, R.J.; Veesler, D. Structural basis for human coronavirus attachment to sialic acid receptors. Nat. Struct. Mol. Biol.,  2019, 26(6), 481-489.
[http://dx.doi.org/10.1038/s41594-019-0233-y] [PMID: 31160783] 
[80] 
Hulswit, R.J.; de Haan, C.A.; Bosch, B.J.de; Haan, C.A.; Bosch, B.J. Coronavirus spike protein and tropism changes. Adv. Virus Res.,  2016, 96, 29-57.
[http://dx.doi.org/10.1016/bs.aivir.2016.08.004] [PMID: 27712627] 
[81] 
Durai, P.; Batool, M.; Shah, M.; Choi, S. Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control. Exp. Mol. Med.,  2015, 47, e181.
[http://dx.doi.org/10.1038/emm.2015.76] [PMID: 26315600] 
[82] 
Ratia, K.; Kilianski, A.; Baez-Santos, Y.M.; Baker, S.C.; Mesecar, A. Structural basis for the ubiquitin-linkage specificity and deISGylating activity of SARS-CoV papain-like protease. PLoS Pathog.,  2014, 10(5), e1004113.
[http://dx.doi.org/10.1371/journal.ppat.1004113] [PMID: 24854014] 
[83] 
Sulea, T.; Lindner, H.A.; Purisima, E.O.; Ménard, R. Deubiquitination, a new function of the severe acute respiratory syndrome coronavirus papain-like protease? J. Virol.,  2005, 79(7), 4550-4551.
[http://dx.doi.org/10.1128/JVI.79.7.4550-4551.2005] [PMID: 15767458] 
[84] 
Báez-Santos, Y.M.; St John, S.E.; Mesecar, A.D. The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res.,  2015, 115, 21-38.
[http://dx.doi.org/10.1016/j.antiviral.2014.12.015] [PMID: 25554382] 
[85] 
Ganeshpurkar, A.; Gutti, G.; Singh, S.K. RNA-dependent RNA polymerases and their emerging roles in antiviral therapy. Viral polymerases: Structures, functions, and roles as antiviral drug targets. Eur. J. Med. Chem.,  2019, 2019, 1-42.
[86] 
Kurokawa, M.; Ochiai, H.; Nagasaka, K.; Neki, M.; Xu, H.; Kadota, S.; Sutardjo, S.; Matsumoto, T.; Namba, T.; Shiraki, K. Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice. Antiviral Res.,  1993, 22(2-3), 175-188.
[http://dx.doi.org/10.1016/0166-3542(93)90094-Y] [PMID: 8279811] 
[87] 
Calland, N.; Dubuisson, J.; Rouillé, Y.; Séron, K. Hepatitis C virus and natural compounds: A new antiviral approach? Viruses,  2012, 4(10), 2197-2217.
[http://dx.doi.org/10.3390/v4102197] [PMID: 23202460] 
[88] 
Du, J.; He, Z.D.; Jiang, R.W.; Ye, W.C.; Xu, H.X.; But, P.P. Antiviral flavonoids from the root bark of Morus alba L. Phytochemistry,  2003, 62(8), 1235-1238.
[http://dx.doi.org/10.1016/S0031-9422(02)00753-7] [PMID: 12648543] 
[89] 
Xu, H.X.; Lee, S.H.; Lee, S.F.; White, R.L.; Blay, J. Isolation and characterization of an anti-HSV polysaccharide from Prunella vulgaris. Antiviral Res.,  1999, 44(1), 43-54.
[http://dx.doi.org/10.1016/S0166-3542(99)00053-4] [PMID: 10588332] 
[90] 
Xu, H.X.; Kadota, S.; Wang, H.; Kurokawa, M.; Shiraki, K.; Matsumoto, T. A new hydrolyzable tannin from Geum japonicum and its antiviral activity. Heterocycles,  1994, 38, 167-175.
[http://dx.doi.org/10.3987/COM-93-6550] 
[91] 
Xu, H.X.; Kadota, S.; Kurokawa, M.; Shiraki, K.; Matsumoto, T.; Namba, T. Isolation and structure of woodorien, a new glucoside having antiviral activity, from Woodwardia orientalis. Chem. Pharm. Bull. (Tokyo),  1993, 41(10), 1803-1806.
[http://dx.doi.org/10.1248/cpb.41.1803] [PMID: 8281578] 
[92] 
Kannan, S.; Kolandaivel, P. Antiviral potential of natural compounds against influenza virus hemagglutinin. Comput. Biol. Chem.,  2017, 71, 207-218.
[http://dx.doi.org/10.1016/j.compbiolchem.2017.11.001] [PMID: 29149637] 
[93] 
Luganini, A.; Terlizzi, M.E.; Catucci, G.; Gilardi, G.; Maffei, M.E.; Gribaudo, G. The cranberry extract oximacro® exerts in vitro virucidal activity against influenza virus by interfering with hemagglutinin. Front. Microbiol.,  2018, 9, 1826.
[http://dx.doi.org/10.3389/fmicb.2018.01826] [PMID: 30131793] 
[94] 
Xu, H.X.; Zeng, F.Q.; Wan, M.; Sim, K.Y. Anti-HIV triterpene acids from Geum japonicum. J. Nat. Prod.,  1996, 59(7), 643-645.
[http://dx.doi.org/10.1021/np960165e] [PMID: 8759159] 
[95] 
Xu, H.X.; Ming, D.S.; Dong, H.; But, P.P. A new anti-HIV triterpene from Geum japonicum. Chem. Pharm. Bull. (Tokyo),  2000, 48(9), 1367-1369.
[http://dx.doi.org/10.1248/cpb.48.1367] [PMID: 10993241] 
[96] 
Xu, H.X.; Wan, M.; Loh, B.N.; Kon, O.L.; Chow, P.W.; Sim, K.Y. Screening of traditional medicines for their inhibitory activity against HIV-1 protease. Phytother. Res.,  1996, 10, 207-210.
[http://dx.doi.org/10.1002/(SICI)1099-1573(199605)10:3<207:AID-PTR812>3.0.CO;2-U] 
[97] 
Sahuc, M.E.; Sahli, R.; Rivière, C.; Pène, V.; Lavie, M.; Vandeputte, A.; Brodin, P.; Rosenberg, A.R.; Dubuisson, J.; Ksouri, R.; Rouillé, Y.; Sahpaz, S.; Séron, K. Dehydrojuncusol, a natural phenanthrene compound extracted from Juncusmaritimus, is a new inhibitor of hepatitis C virus RNA replication. J. Virol.,  2019, 93(10), e02009-e02018.
[http://dx.doi.org/10.1128/JVI.02009-18] [PMID: 30842319] 
[98] 
Zhang, Y.B.; Luo, D.; Yang, L.; Cheng, W.; He, L.J.; Kuang, G.K.; Li, M.M.; Li, Y.L.; Wang, G.C. Matrine-type alkaloids from the roots of Sophora flavescens and their antiviral activities against the hepatitis B virus. J. Nat. Prod.,  2018, 81(10), 2259-2265.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00576] [PMID: 30298740] 
[99] 
Li, B.; Li, L.; Peng, Z.; Liu, D.; Si, L.; Wang, J.; Yuan, B.; Huang, J.; Proksch, P.; Lin, W. Harzianoic acids A and B, new natural scaffolds with inhibitory effects against hepatitis C virus. Bioorg. Med. Chem.,  2019, 27(3), 560-567.
[http://dx.doi.org/10.1016/j.bmc.2018.12.038] [PMID: 30606673] 
[100] 
Cinatl, J.; Morgenstern, B.; Bauer, G.; Chandra, P.; Rabenau, H.; Doerr, H.W. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet,  2003, 361(9374), 2045-2046.
[http://dx.doi.org/10.1016/S0140-6736(03)13615-X] [PMID: 12814717] 
[101] 
Lin, S.C.; Ho, C.T.; Chuo, W.H.; Li, S.; Wang, T.T.; Lin, C.C. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect. Dis.,  2017, 17(1), 144.
[http://dx.doi.org/10.1186/s12879-017-2253-8] [PMID: 28193191] 
[102] 
Bzówka, M.; Mitusińska, K.; Raczyńska, A.; Samol, A.; Tuszyński, J.A.; Góra, A. Structural and evolutionary analysis indicate that the SARS-COV-2 MPRO is a challenging target for small-molecule inhibitor design. Int. J. Mol. Sci.,  2020, 21(9), 3099.
[http://dx.doi.org/10.3390/ijms21093099] [PMID: 32353978] 
[103] 
Li, G.; De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov.,  2020, 19(3), 149-150.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666] 
[104] 
Morse, J.S.; Lalonde, T.; Xu, S.; Liu, W.R. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. ChemBioChem,  2020, 21(5), 730-738.
[http://dx.doi.org/10.1002/cbic.202000047] [PMID: 32022370] 
[105] 
Khan, T.; Khan, M. Plant in vitro culture technologies; a promise into factories of secondary metabolites against COVID-19. Front. Plant Sci.,  2020, 10, 13140.
[106] 
Yanfang, X. Juan, Zhang.; Zhaoxiang, Bian.; Hua, Zhou.; Zhenbiao, Zhang.; Zhixiu, Lin.; Hongxi, Xu. Bioactive natural compounds against human coronaviruses: A review and perspective. Acta Pharm. Sin. B,  2020, 10, 1163-1174.
[http://dx.doi.org/10.1016/j.apsb.2020.06.002] 
[107] 
Ho, T.Y.; Wu, S.L.; Chen, J.C.; Li, C.C.; Hsiang, C.Y. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res.,  2007, 74(2), 92-101.
[http://dx.doi.org/10.1016/j.antiviral.2006.04.014] [PMID: 16730806] 
[108] 
McKee, D.L.; Sternberg, A.; Stange, U.; Laufer, S.; Naujokat, C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol. Res.,  2020, 157, 104859.
[http://dx.doi.org/10.1016/j.phrs.2020.104859] [PMID: 32360480] 
[109] 
Mhatre, S.; Srivastava, T.; Naik, S.; Patravale, V. Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review. Phytomedicine,  2021, 85, 153286.
[http://dx.doi.org/10.1016/j.phymed.2020.153286] [PMID: 32741697] 
[110] 
Park, J.Y.; Ko, J.A.; Kim, D.W.; Kim, Y.M.; Kwon, H.J.; Jeong, H.J.; Kim, C.Y.; Park, K.H.; Lee, W.S.; Ryu, Y.B. Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV. J. Enzyme Inhib. Med. Chem.,  2016, 31(1), 23-30.
[http://dx.doi.org/10.3109/14756366.2014.1003215] [PMID: 25683083] 
[111] 
Wahyuni, T.S.; Utsubo, C.A.; Hotta, H. Promising anti-hepatitis C virus compounds from natural resources. Nat. Prod. Commun.,  2016, 11(8), 1193-1200.
[http://dx.doi.org/10.1177/1934578X1601100840] [PMID: 30725589] 
[112] 
Liu, L.; Hu, Y.; Shen, Y.F.; Wang, G.X.; Zhu, B. Evaluation on antiviral activity of coumarin derivatives against spring viraemia of carp virus in epithelioma papulosum cyprini cells. Antiviral Res.,  2017, 144, 173-185.
[http://dx.doi.org/10.1016/j.antiviral.2017.06.007] [PMID: 28624462] 
[113] 
Hu, Y.; Chen, W.; Shen, Y.; Zhu, B.; Wang, G.X. Synthesis and antiviral activity of coumarin derivatives against infectious hematopoietic necrosis virus. Bioorg. Med. Chem. Lett.,  2019, 29(14), 1749-1755.
[http://dx.doi.org/10.1016/j.bmcl.2019.05.019] [PMID: 31104994] 
[114] 
Al-Amiery, A.A.; Kadhum, A.A.H.; Mohamad, A.B. Antifungal activities of new coumarins. Molecules,  2012, 17(5), 5713-5723.
[http://dx.doi.org/10.3390/molecules17055713] [PMID: 22628043] 
[115] 
Matos, M.; Vina, J.; Janeiro, D.; Borges, P.; Santana, F.; Uriarte, E. Bioorg. Med. Chem. Lett.,  2010, 20, 51-57.
[116] 
Maja, M.; Čačić, C. Antioxidant activity of some (7-hydroxy-2- oxo-2Hchromen-4yl) acetic acid derivatives. Croat. J. Food Sci. Technol.,  2012, 4, 54-63.
[117] 
Khan. Yusufzai, S. Osman, H.; Khan, M.S.; Mohamad, S.; Sulaiman, O.; Parumasivam, T.; Johansah, N. Design, characterization, in vitro antibacterial, antitubercular evaluation and structure-activity relationships of new hydrazinyl thiazolyl coumarin derivatives. Med. Chem. Res.,  2017, 26, 1139-1148.
[http://dx.doi.org/10.1007/s00044-017-1820-2] 
[118] 
Yusufzai, S.K.; Osman, H.; Khan, M.S.; Abd Razik, B.M.; Ezzat, M.O.; Mohamad, S.; Sulaiman, O.; Gansau, J.A.; Parumasivam, T. 4-Thiazolidinone coumarin derivatives as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors: Synthesis, molecular docking, biological evaluation and structure-activity relationship studies. Chem. Cent. J.,  2018, 12(1), 69.
[http://dx.doi.org/10.1186/s13065-018-0435-0] [PMID: 29896651] 
[119] 
Gresele, P.; Agnelli, G. Novel approaches to the treatment of thrombosis. Trends Pharmacol. Sci.,  2002, 23(1), 25-32.
[http://dx.doi.org/10.1016/S0165-6147(00)01885-X] [PMID: 11804648] 
[120] 
Weitz, J.I.; Linkins, L.A. Beyond heparin and warfarin: The new generation of anticoagulants. Expert Opin. Investig. Drugs,  2007, 16(3), 271-282.
[http://dx.doi.org/10.1517/13543784.16.3.271] [PMID: 17302522] 
[121] 
Vacca, J.P. Functional diversity of compound libraries. Curr. Opin. Chem. Biol.,  2000, 43, 94.
[122] 
Andronati, S.A.; Karaseva, T.L.; Krysko, A.A. Peptidomimetics - antagonists of the fibrinogen receptors: molecular design, structures, properties and therapeutic applications. Curr. Med. Chem.,  2004, 11(9), 1183-1211.
[http://dx.doi.org/10.2174/0929867043365314] [PMID: 15134514] 
[123] 
Chackalamannil, S.; Wang, Y.; Greenlee, W.J.; Hu, Z.; Xia, Y.; Ahn, H.S.; Boykow, G.; Hsieh, Y.; Palamanda, J.; Agans-Fantuzzi, J.; Kurowski, S.; Graziano, M.; Chintala, M. Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J. Med. Chem.,  2008, 51(11), 3061-3064.
[http://dx.doi.org/10.1021/jm800180e] [PMID: 18447380] 
[124] 
Sashidhara, K.V.; Palnati, G.R.; Avula, S.R.; Singh, S.; Jain, M.; Dikshit, M. Synthesis and evaluation of anti-thrombotic activity of benzocoumarin amide derivatives. Bioorg. Med. Chem. Lett.,  2012, 22(9), 3115-3121.
[http://dx.doi.org/10.1016/j.bmcl.2012.03.059] [PMID: 22483393] 
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DOI https://dx.doi.org/10.2174/1389557521666211116120823	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607
Mini-Reviews in Medicinal Chemistry

Therapeutic Journey and Recent Advances in the Synthesis of Coumarin Derivatives

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