Abstract
Since the discovery of dicoumarol (a coumarin-based anticoagulant) in 1940, coumarins have been found to possess a range of biological activities such as antimicrobial, anti-inflammatory, antioxidant, anticancer, and antiviral. The subsequent development of compounds containing a coumarin nucleus for use as potential new drug candidates has progressively grown in view of their diverse biological activities. This review addresses the structure–activity relationship of coumarin-based compounds, focusing on their potential for use as antiprotozoal agents against neglected tropical diseases which are a diverse group of illnesses that affect over one billion people globally. Most of them are caused by parasitic organisms including protozoa, helminths, and ectoparasites. Neglected tropical diseases which are caused by protozoa include human leishmaniasis, Chagas disease, American trypanosomiasis, and African trypanosomiasis, which range in severity from mild and self-curing to untreatable and fatal. This review compiles relevant information on the biological potential and possible mechanisms of action of coumarin-based compounds for use against neglected tropical diseases, including malaria, and highlights the most relevant and promising compounds. Natural, synthetic, and semi-synthetic coumarin represent prominent candidates in the search for new drugs to treat neglected tropical diseases.
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18 October 2021
A Correction to this paper has been published: https://doi.org/10.1007/s43450-021-00188-9
References
Al-Majedy YK, Kadhum AAH, Al-Amiery AAH, Mohamed AB (2017) Coumarins: the antimicrobial agents. Sys Rev Pharm 8:62–70. https://doi.org/10.5530/srp.2017.1.11
Akendengue B, Ngou-Milama E, Laurens A, Hocquemiller R (1999) Recent advances in the fight against leishmaniasis with natural products. Parasite 6:3–8. https://doi.org/10.1051/parasite/1999061003
Akkol EK, Genç Y, Karpuz B, Sobarzo-Sánchez E, Capasso R (2020) Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers 12:1959–1984. https://doi.org/10.3390/cancers12071959
Al-Warhi T, Sabt A, Elkaeed EB, Eldehna WM (2020) Recent advancements of coumarin-based anticancer agents: an up-to-date review. Bioorg Chem 103:104163. https://doi.org/10.1016/j.bioorg.2020.104163
Andrews KT, Fisher G, Skinner-Adams TS (2014) Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist 4:95–111. https://doi.org/10.1016/j.ijpddr.2014.02.002
Bairagi S, Salaskar PP, Loke SD, Surve NN, Tandel DV, Dusura MD (2012) Medicinal significance of coumarins: a review. Int J Pharm Sci Res 4:16–19
Balogun EO, Inaoka DK, Shiba T, Tsuge C, May B, Sato T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PAM, Watanabe Y, Moore AL, Harada S, Kita K (2019) Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei. FASEB J 33:13002–13013. https://doi.org/10.1096/fj.201901342R
Belluti F, Uliassi E, Veronesi G, Bergamini C, Kaiser M, Brun R, Viola A, Fato R, Michels PAM, Krauth-Siegel RL, Cavalli A, Bolognesi ML (2014) Toward the development of dual-targeted glyceraldehydes-3-phosphate dehydrogenase/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi. Chem Med Chem 9:371–382. https://doi.org/10.1002/cmdc.201300399
Boitz JM, Ullman B (2010) Amplification of adenine phosphoribosyltransferase suppresses the conditionally lethal growth and virulence phenotype of Leishmania donovani mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases. J Biol Chem 24:18555–18564. https://doi.org/10.1074/jbc.M110.125393
Brancaglion GA, Toyota AE, Machado JVC, Júnior JJF, Silveira AT, Boas DFV, Santos EGD, Caldas IS, Carvalho DT (2018) In vitro and in vivo trypanocidal activities of 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-cromen-2-one, a new synthetic coumarin of low cytotoxicity against mammalian cells. Chem Biol Drug Des 92:1888–1898. https://doi.org/10.1111/cbdd.13362
Brun R, Blum J, Chappuis F, Burri C (2010) Human African trypanosomiasis. Lancet 375:148–159. https://doi.org/10.1016/S0140-6736(09)60829-1
Carneiro A, Matos MJ, Uriarte E, Santana L (2021) Trending topics on coumarin and its derivatives in 2020. Molecules 26:501–516. https://doi.org/10.3390/molecules26020501
Cheuka PM, Mayoka G, Mutai P, Chibale K (2016) The role of natural products in drug discovery and development against neglected tropical diseases. Molecules 22:58. https://doi.org/10.3390/molecules22010058
Coelho GS, Andrade JS, Xavier VF, Junior PAS, Araujo BCR, Fonseca KDS, Caetano MS, Murta SMF, Vieira PM, Carneiro CM, Taylor JG (2019) Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi. Chem Biol Drug Des 93:337–350. https://doi.org/10.1111/cbdd.13420
Cowman AF, Healer J, Marapana D, Marsh K (2016) Malaria: biology and disease. Cell 167:610–624. https://doi.org/10.1016/j.cell.2016.07.055
Cui L, Su X-Z (2009) Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev Anti Infect Ther 7:999–1013. https://doi.org/10.1586/eri.09.68
Cunningham ML, Beverley SM (2001) Pteridine salvage throughout the Leishmania infectious cycle: implications for antifolate chemotherapy. Mol Biochem Parasitol 113:199–213. https://doi.org/10.1016/s0166-6851(01)00213-4
Davis RA, Vullo D, Maresca A, Supuran CT, Pulsen SA (2012) Natural product coumarins that inhibit human carbonic anhydrases. Bioorg Med Chem 21:1539–1543. https://doi.org/10.1016/j.bmc.2012.07.021
Fampa P, Florencio M, Santana RC, Rosa D, Soares DC, de Matos Guedes HL, da Silva AC, Chaves DS, Pinto-da-Silva LH (2021) Anti-Leishmania effects of volatile oils and their isolates. Rev Bras Farmacogn. https://doi.org/10.1007/s43450-021-00146-5
Field MC, Fairlamb AH, Ferguson MAJ, Gray DW, Read KD, Rycker MD, Torrie LS, Wyatt PG, Wyllie S, Gilbert IH (2017) Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nat Rev Microbiol 15:217–231. https://doi.org/10.1038/nrmicro.2016.193
Foroozesh M, Sridhar J, Goyal N, Liu J (2019) Coumarins and P450s, studies reported to-date. Molecules 24:1620. https://doi.org/10.3390/molecules24081620
Freitas RF, Prokopczyk IM, Zottis A, Oliva G, Andricopulo AD, Trevisan MTS, Vilegas W, Silva MGV, Montanari CA (2009) Discovery of novel Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase inhibitors. Bioorg Med Chem 17:2476–2482. https://doi.org/10.1016/j.bmc.2009.01.079
Gao Y, Cheng H, Khan S, Xiao G, Rong L, Bai C (2020) Development of coumarin derivatives as potent anti-filovirus entry inhibitors targeting viral glycoprotein. Eur J Med Chem 204:112595. https://doi.org/10.1016/j.ejmech.2020.112595
Gonçalves GA, Spillere AR, Neves GMd, Kagami LP, Poser GLv, Canto RFS, Eifler-Lima VL (2020) Natural and synthetic coumarins as antileishmanial agents: a review. Eur J Med Chem 203:112514. https://doi.org/10.1016/j.ejmech.2020.112514
Gong XR, Xi GL, Liu ZQ (2015) Activity of coumarin oxadiazole appended phenol in inhibiting DNA oxidation and scavenging radical. Tetrahedron Lett 56:6257–6261. https://doi.org/10.1016/j.tetlet.2015.09.105
Goud NS, Kumar P, Bharath RW (2020) Recent developments of target based coumarin derivatives as potential anticancer agents. Mini Rev Med Chem 20:1754–17668. https://doi.org/10.2174/1389557520666200510000718
Gu J, Gui Y, Chen L, Yuan G, Lu H-Z, Xu X (2013) Use of natural products as chemical library for drug discovery and network pharmacology. PloS One 8:e62839. https://doi.org/10.1371/journal.pone.0062839
Guiñez RF, Matos MJ, Vazquez-Rodriguez S, Santana L, Uriarte E, Olea-Azar C, Maya JD (2013) Synthesis and evaluation of antioxidant and trypanocidal properties of a selected series of coumarin derivatives. Future Med Chem 5:1911–1922. https://doi.org/10.4155/fmc.13.147
Guiñez RF, Matos MJ, Vazquez-Rodriguez S, Santana L, Uriarte E, Borges F, Olea-Azar C, Maya JD (2015) Interest of antioxidant agents in parasitic diseases. The case study of coumarins. Curr Top Med Chem 15:850–856. https://doi.org/10.2174/1568026615666150220113155
Gupta S, Khan J, Kumari P, Narayana C, Ayana R, Chakrabarti M, Sagar R, Singh S (2019) Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential. Malar J 18:346. https://doi.org/10.1186/s12936-019-2971-z
Hall BS, Bot C, Wilkinson SR (2011) Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J Biol Chem 286:13088–13095. https://doi.org/10.1074/jbc.M111.230847
Hotez PJ, Aksoy S, Brindley PJ, Kamhawi S (2020) What constitutes a neglected tropical disease? PLoS Negl Trop Dis 14:e0008001. https://doi.org/10.1371/journal.pntd.0008001
Hu X-L, Gao C, Xu Z, Liu M-L, Feng L-S, Zhang G-d (2018) Recent development of coumarin derivatives as potential antiplasmodial and antimalarial agents. Curr Top Med Chem 18:114–123. https://doi.org/10.2174/1568026618666171215101158
Huang F, Tang L-H, Yu L-Q, Ni Y-C, Wang Q-M, Nan F-J (2006) In vitro potentiation of antimalarial activities by daphnetin derivatives against Plasmodium falciparum. Biomed Environ Sci 19:367–370 (PMID:17190189)
Iranshahi M, Askari M, Sahebkar A, Hadjipavlou-Litina D (2009) Evaluation of antioxidant, anti-inflammatory and lipoxygenase inhibitory activities of the prenylated coumarin umbelliprenin. DARU: J Pharm Sci 17:99–103
Kalaria PN, Satasia SP, Raval DK (2014) Synthesis, characterization and biological screening of novel 5-imidazopyrazole incorporated fused pyran motifs under microwave irradiation. New J Chem 38:1512–1521. https://doi.org/10.1039/C3NJ01327H
Katsuno K, Burrows JN, Duncan K, Huijsduijnen RHV, Kaneko T, Kita K, Mowbray CE, Schmatz D, Warner P, Slingsby BT (2015) Hit and lead criteria in drug discovery for infectious diseases of the developing world. Nat Rev Drug Discov 14:751–758. https://doi.org/10.1038/nrd4683
Khalid SA, Farouk A, Geaary TG, Jensen JB (1986) Potential antimalarial candidates from African plants: an in vitro approach using Plasmodium falciparum. J Ethnopharmacol 15:201–209. https://doi.org/10.1016/0378-8741(86)90156-X
Krishna S, Kleine C, Stich A (2020) African Trypanosomiasis. Hunter’s Tropical Medicine and Emerging Infectious Diseases. 755–761. https://doi.org/10.1016/B978-0-323-55512-8.00102-2
López-Vélez R, Norman FF, Bern C (2020) American trypanosomiasis (Chagas disease) In: Ryan ET, Hill DR, Solomon T, Aronson NE, Endy TP (eds) Hunter’s tropical medicine and emerging infectious diseases. pp 762–775. https://doi.org/10.1016/B978-0-323-55512-8.00103-4
Mandlik V, Patil S, Bopanna R, Basu S, Singh S (2016) Biological activity of coumarin derivatives as anti-leishmanial agents. PloS One 11:e0164585. https://doi.org/10.1371/journal.pone.0164585
Maresca A, Temperini C, Pochet L, Masereel B, Scozzafava A, Supuran CT (2010) Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. J Med Chem 53:335–344. https://doi.org/10.1021/jm901287j
Moreira W, Légaré D, Racine G, Roy G, Ouellette M (2014) Proteomic analysis of metacyclogenesis in Leishmania infantum wild-type and ptr1 null mutant. EuPA Open Proteom 4:171–183. https://doi.org/10.1016/j.euprot.2014.07.003
Mu LY, Wang QM, Ni YC (2002) In vitro antimalarial effect of daphnetin relating to its iron-chelating activity. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi (Chinese Journal of Parasitology & Parasitic Diseases) 20:83–85
Mu LY, Wang QM, Ni YC (2003) Effect of daphnetin on SOD activity and DNA synthesis of Plasmodium falciparum in vitro. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi (Chinese Journal of Parasitology & Parasitic Diseases) 21:157–159
Murray RDH, Méndez J, Brown SA (1982) The natural coumarins: occurrence, chemistry and biochemistry. Wiley, University of Michigan, p 702
Newman J, Cragg GM (2020) Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod 83:770–803. https://doi.org/10.1021/acs.jnatprod.9b01285
Ojha PK, Kumar V, Roy J, Roy K (2021) Recent advances in quantitative structure-activity relationship models of antimalarial drugs. Expert Opin Drug Discov 16:659–695. https://doi.org/10.1080/17460441.2021.1866535
Oketch-Rabah HA, Mwangi JW, Lisgarten J, Mberu EK (2000) A new antiplasmodial coumarin from Toddalia asiatica roots. Fitoterapia 71:636–640. https://doi.org/10.1016/s0367-326x(00)00222-7
Oliaro-Bosso S, Viola F, Matsuda S, Cravotto G, Tagliapietra S, Balliano G (2004) Umbelliferone aminoalkyl derivatives as inhibitors of oxidosqualene cyclases from Saccharomyces cerevisiae, Trypanosoma cruzi, and Pneumocystis carinii. Lipids 39:1007–1012. https://doi.org/10.1007/s11745-004-1323-2
Oliaro-Bosso S, Viola F, Taramino S, Tagliapietra S, Barge A, Cravotto G, Balliano G (2007) Inhibitory effect of umbelliferone aminoalkyl derivatives on oxidosqualene cyclases from S. cerevisiae, T. cruzi, P. carinii, H. sapiens, and A. thaliana: a structure-activity study. Chem Med Chem 2:226–233. https://doi.org/10.1002/cmdc.200600234
O’Neill PM, Barton VE, Ward SA (2010) The molecular mechanism of action of artemisinin-the debate continues. Molecules 15:1705–1721. https://doi.org/10.3390/molecules15031705
Patterson S, Wyllie S (2014) Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects. Trends Parasitol 30:289–298. https://doi.org/10.1016/j.pt.2014.04.003
Pavão F, Castilho MS, Pupo MT, Dias RLA, Correa AG, Fernandes JB, Silva MFGFd, Mafezoli J, Vieira PC, Oliva G (2002) Structure of Trypanosoma cruzi glycosomal glyceraldehydes-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95Å resolution. FEBS Lett 520:13–17. https://doi.org/10.1016/s0014-5793(02)02700-x
Pedreira JG, Franco LS, Barreiro EJ (2019) Chemical intuition in drug design and discovery. Curr Top Med Chem 19:1679–1693. https://doi.org/10.2174/1568026619666190620144142
Pérez-Molina JA, Molina I (2018) Chagas disease. Lancet 391:82–94. https://doi.org/10.1016/S0140-6736(17)31612-4
Perkin WH (1868) On the artificial production of coumarin and formation of its homologues. J Chem Soc 21:53–63. https://doi.org/10.1039/js8682100053
Podbielkowska M, Piwocka M, Waszkowska E, Waleza M, Zobel AM (1995) Effect of coumarin and its derivatives on mitosis and ultrastructure of meristematic cells. Int J Pharmacogn 33:7–15. https://doi.org/10.3109/13880209509088140
Posner GW, O’Neill PM (2004) Knowledge of the proposed chemical mechanism of action and cytochrome p450 metabolism of antimalarial trioxanes like artemisinin allows rational design of new antimalarial peroxides. Acc Chem Res 37:397–404. https://doi.org/10.1021/ar020227u
Pramanik PK, Alam MN, Chowdhury DR, Chakraborti T (2019) Drug resistance in protozoan parasites: an incessant wrestle for survival. J Glob Antimicrob Resist 18:1–11. https://doi.org/10.1016/j.jgar.2019.01.023
Robledo-O’Ryan N, Matos MJ, Vazquez-Rodriguez S, Santana L, Uriarte E, Moncada-Basualto M, Mura F, Lapier M, Maya JD, Olea-Azar C (2017) Synthesis, antioxidant and antichagasic properties of a selected series of hydroxy-3-arylcoumarins. Bioorg Med Chem 25:621–632. https://doi.org/10.1016/j.bmc.2016.11.033
Robello C, Maldonado DP, Hevia A, Hoashi M, Frattaroli P, Montacutti V, Heguy A, Dolgalev I, Mojica M, Iraola G, Dominguez-Bello MG (2019) The fecal, oral and skin microbiota of children with chagas disease treated with benznidazole. PloS One 14:e0212593. https://doi.org/10.1371/journal.pone.0212593
Rodríguez-Hernández KD, Martínez I, Agredano-Moreno LT, Jiménez-García LF, Reyes-Chilpa R, Espinoza B (2019) Coumarins isolated from Calophyllum brasiliense produce ultrastructural alterations and affect in vitro infectivity of Trypanosoma cruzi. Phytomedicine 61:152827. https://doi.org/10.1016/j.phymed.2019.152827
Rodríguez-Hernández KD, Martínez I, Reyes-Chilpa R, Espinoza B (2020) Mammea type coumarins isolated from Calophyllum brasiliense induced apoptotic cell death of Trypanosoma cruzi through mitochondrial dysfunction, ROS production and cell cycle alterations. Bioorg Chem 100:103894. https://doi.org/10.1016/j.bioorg.2020.103894
Rosa JMC, Quesada MEC (2017) Optimization of prototypes. In: De Gruyter (ed) Pharmaceutical chemistry, volume 1 - drug design and action. Berlin, pp 46–69. https://doi.org/10.1515/9783110528480-005
Salomon CJ (2012) First century of Chagas’ disease: an overview on novel approaches to nifurtimox and benznidazole delivery systems. J Pharm Sci 101:888–894. https://doi.org/10.1002/jps.23010
Sajjadi SE, Pestechian N, Kazemi M, Mohaghegh MA, Hosseini-Safa A (2016a) Evaluation of the antimalarial effect of Ferulago angulata (Schlecht.) Boiss extract and suberosin epoxide against Plasmodium berghei in comparison with chloroquine using in-vivo test. Iran J Pharm Res 15:515–521
Sajjadi SE, Eskandarian AA, Shokoohinia Y, Yousefi HA, Mansourian M, Asgarian-Nasab H, Mohseni N (2016b) Antileishmanial activity of prenylated coumarins isolated from Ferulago angulata and Prangos asperula. Res Pharm Sci 11:324–331. https://doi.org/10.4103/1735-5362.189314
Sangshetti JN, Khan FAK, Kulkarni AA, Patil RH, Pachpinde AM, Lohar KS, Shinde DB (2016) Antileishmanial activity of novel indolyl–coumarin hybrids: design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction. Bioorg Med Chem Lett 26:829–835. https://doi.org/10.1016/j.bmcl.2015.12.085
Sashidhara K, Kumar A, Dodda RP, Krishna NN, Agarwal P, Srivastava K, Puri SK (2012) Coumarin–trioxane hybrids: synthesis and evaluation as a new class of antimalarial scaffolds. Bioorg Med Chem Lett 22:3926–3930. https://doi.org/10.1016/j.bmcl.2012.04.100
Smith HJ, Meremikwu MM (2003) Iron-chelating agents for treating malaria. Cochrane Database Syst Rev 2:CD001474. https://doi.org/10.1002/14651858.CD001474
Song XF, Fan J, Liu L, Liu XF, Gao F (2020) Coumarin derivatives with anticancer activities: an update. Arch Pharm 353:e2000025. https://doi.org/10.1002/ardp.202000025
Stefanachi A, Leonetti F, Pisani L, Catto M, Carotti A (2018) Coumarin: a natural, privileged and versatile scaffold for bioactive compounds. Molecules 23:250. https://doi.org/10.3390/molecules23020250
Sundar S, Chakravarty J, Meena LP (2019) Leishmaniasis: treatment, drug resistance and emerging therapies. Expert Opin Orphan Drugs 7:1–10. https://doi.org/10.1080/21678707.2019.1552853
Susidarti RA, Mustofa, Lusika VP, Astana YN (2014) In vitro antiplasmodial activity of coumarin 8-hydroxyisocapnolactone-2’,3’-diol isolated from Micromelum minutum (G. Forst.) Wight & Arn. Indonesian J Pharm 25:44–50. https://doi.org/10.14499/indonesianjpharm25iss1pp44
Ullah N, Nadhman A, Siddiq S, Mehwish S, Islam A, Jafri L, Hamayun M (2016) Plants as antileishmanial agents: current scenario. Phytother Res 30:1905–1925. https://doi.org/10.1002/ptr.5710
Vazquez-Rodriguez S, Guíñez RF, Matos MJ, Olea-Azar C, Maya JD, Uriarte E, Santana L (2016) Facing Chagas’ disease: trypanocidal properties of new coumarin chalcone scaffolds. Med Chem 12:537–543. https://doi.org/10.2174/1573406412666160107111809
Vieira PC, Mafezoli J, Pupo MT, Fernandes JB, Silva MFdGF, Albuquerque S, Oliva G, Pavão F (2001) Strategies for the isolation and identification of trypanocidal compounds from the Rutales. Pure Appl Chem 73:617–622. https://doi.org/10.1351/pac200173030617
Vila-nova NS, Morais SM, Falcão MJC, Bevilaqua CML, Rondon FCM, Wilson ME, Vieira IGP, Andrade HF (2012) Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome. Pesq Vet Bras 32:1164e–11168. https://doi.org/10.1590/S0100-736X2012001100015
Veeresham C (2012) Natural products derived from plants as a source of drugs. J Adv Pharm Technol Res 3:200–201. https://doi.org/10.4103/2231-4040.104709
Venugopala KN, Rashmi V, Odhav B (2013) Review on natural coumarin lead compounds for their pharmacological activity. Biomed Res Int 2013:963248. https://doi.org/10.1155/2013/963248
Vogel A (1820) Darstellung von benzoesäure aus der tonka-bohne und aus den meliloten- oder steinklee-blumen. Annalen Der Physik 64:161–166. https://doi.org/10.1002/andp.18200640205
Wang QM, Ni YC, Xu YQ, Ha SH, Cai Y (2000) The schizontocidal activity of daphnetin against malaria parasites in vitro and in vivo. Chin J Parasitol Parasit Dis 18:204–206
Wang G, Pang J, Hu X, Nie T, Lu X, Li X, Wang X, Lu Y, Yang X, Jiang J, Li C, Xiong YQ, You XF (2019) Daphnetin: a novel anti-Helicobacter pylori agent. Int J Mol Sci 20:850. https://doi.org/10.3390/ijms20040850
Whittaker C, Slater H, Nash R, Bousema T, Drakeley C, Ghani AC, Okell LC (2021) Global patterns of submicroscopic Plasmodium falciparum malaria infection: insights from a systematic review and meta-analysis of population surveys. Lancet Microbe. https://doi.org/10.1016/S2666-5247(21)00055-0
WHO (2020a) World Health Organisation Factsheet: Neglected Zoonotic Diseases Available Online at: https://www.who.int/teams/control-of-neglected-tropical-diseases/neglected-zoonotic-diseases. Accessed 9 Apr 2021
WHO (2020b) World Health Organisation Factsheet: Leishmaniasis. Available Online at: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed 9 Apr 2021
WHO (2020c) World Health Organisation Factsheet: Chagas Disease (also known as American Trypanosomiasis Available Online at: https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis). Accessed 9 Apr 2021
WHO (2020d) World Health Organisation Factsheet: Trypanosomiasis, Human African (sleeping sickness) Available Online at: https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness). Accessed 9 Apr 2021
WHO (2020e) World Health Organisation Factsheet: Malaria Available Online at: https://www.who.int/news-room/fact-sheets/detail/malaria. Accessed 9 Apr 2021
Yadav N, Agarwal D, Kumar S, Dixit AK, Gupta RD, Awasthi SK (2018) In vitro antiplasmodial efficacy of synthetic coumarin-triazole analogs. Eur J Med Chem 145:735–745. https://doi.org/10.1016/j.ejmech.2018.01.017
Yang YZ, Ranz A, Pan HZ, Zhang ZN, Lin XB, Meshnick SR (1992) Daphnetin: a novel antimalarial agent with in vitro and in vivo activity. Am J Trop Med Hyg 46:15–20. https://doi.org/10.4269/ajtmh.1992.46.15
Zaheer Z, Khan FAK, Sangshetti JN, Patil RH (2015) Efficient one-pot synthesis, molecular docking and in silico ADME prediction of bis-(4-hydroxycoumarin-3-yl) methane derivatives as antileishmanial agents. EXCLI J 14:935–947. https://doi.org/10.17179/excli2015-244
Zaheer Z, Khan FAK, Sangshetti JN, Patil RH (2016) Expeditious synthesis, antileishmanial and antioxidant activities of novel 3-substituted-4-hydroxycoumarin derivatives. Chin Chem Lett 27:287–294. https://doi.org/10.1016/j.cclet.2015.10.028
Zhu M, Ma L, Wen J, Dong B, Wang Y, Wang Z, Zhou J, Zhang G, Wang J, Guo Y, Liang C, Cen S, Wang Y (2020) Rational design and structure-activity relationship of coumarin derivatives effective on HIV-1 protease and partially on HIV-1 reverse transcriptase. Eur J Med Chem 186:111900. https://doi.org/10.1016/j.ejmech.2019.111900
Zobel AM, Brown SA (1989) Localization of daphnetin and umbelliferone in different tissues of Daphne mezereum shoots. Can J Bot 67:1456–1459. https://doi.org/10.1139/b89-194
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This study was fnancially supported by the Universidade Federal de Alfenas under the “PIB-Pós Scholarship” and was also fnanced in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001 and by the “Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)”, under Process Number APQ-00686–18. The authors wish to acknowledge and thank both parties for their financial support.
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The role of each author involved in the development of this study is as follows: The conception and design of the study was carried out by DTC, LFD, ISC, and JAH. The literature searching and data collection was performed by EJTS and CFC. The analysis and interpretation of the literature search data was conducted by LFD, ISC, JAH, and DTC. Drafting the manuscript was done by EJTS, CFC, LFD, ISC, and DTC. Critical revision of the manuscript was carried out by JAH and DTC. All the authors have read the final manuscript and approved the submission.
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This article is part of a Special Issue to celebrate the 35th anniversary of the Brazilian Journal of Pharmacognosy
The original online version of this article was revised to the correct the size of the chemical structures and the funding information will be updated to appear as: Funding This study was fnancially supported by the Universidade Federal de Alfenas under the “PIB-Pós Scholarship” and was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001 and by the "Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)", under Process Number APQ-00686-18. The authors wish to acknowledge and thank both parties for their financial support.
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Sierra, E.J.T., Cordeiro, C.F., de Figueiredo Diniz, L. et al. Coumarins as Potential Antiprotozoal Agents: Biological Activities and Mechanism of Action. Rev. Bras. Farmacogn. 31, 592–611 (2021). https://doi.org/10.1007/s43450-021-00169-y
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DOI: https://doi.org/10.1007/s43450-021-00169-y