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Mini-Reviews in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

Mini-Review Article

Pyrazole as an Anti-Microbial Scaffold: A Comprehensive Review

Author(s): Parminder Kaur* and Vimal Arora

Volume 20, Issue 6, 2023

Published on: 08 December, 2022

Page: [578 - 592] Pages: 15

DOI: 10.2174/1570193X20666221031100542

Price: $65

Abstract

Pathogenic microorganisms cause serious and lethal infectious diseases. Numerous antimicrobial agents have been developed during the last few decades to treat these infectious diseases, but these are still expanding worldwide. Moreover, microorganisms are developing resistance against commercially available medicines. So, antimicrobial resistance is expanding as the most serious health threat particularly in developing countries, due to the easier availability of anti-microbial drugs. Therefore, the scarcity of effective antibiotics suggests the pressing demand for new anti-microbial agents. Modern drug discovery regarded heterocyclic compounds as its core due to their striking structural characteristics. Pyrazole is considered as a significant heterocyclic nucleus in modern drug development. This review brings a considerable summary regarding derivatives of pyrazole developed over the last decade for their anti-microbial action, along with docking studies carrying an expectation that it will be beneficial for medicinal chemists working in anti-microbial drug development.

Graphical Abstract

[1]
Serban, G.; Stanasel, O.; Serban, E.; Bota, S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Des. Devel. Ther., 2018, 12, 1545-1566.
[http://dx.doi.org/10.2147/DDDT.S155958] [PMID: 29910602]
[2]
Kaur, P. 1,2,4-Triazole as an antimicrobial scaffold. J. Pharm. Res. Ther., 2020, 1(02), 62-70.
[3]
Bansal, A. A brief review on antimicrobial potential of pyrazoles (From 2010-2018). Mini Rev. Org. Chem., 2020, 17(2), 197-222.
[http://dx.doi.org/10.2174/1570193X16666190122162920]
[4]
Verma, R.; Verma, S.K.; Rakesh, K.P.; Girish, Y.R.; Ashrafizadeh, M.; Sharath Kumar, K.S.; Rangappa, K.S. Pyrazole-based analogs as potential antibacterial agents against methicillin-resistance Staphylococcus aureus (MRSA) and its SAR elucidation. Eur. J. Med. Chem., 2021, 212, 113134.
[http://dx.doi.org/10.1016/j.ejmech.2020.113134] [PMID: 33395624]
[5]
Antimicrobial resistance. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (Accessed on: April 29, 2022).
[6]
Alam, A. M. Antibacterial pyrazoles: Tackling resistant bacteria. Future Med. Chem., 2022, 14(5), 343-362.
[http://dx.doi.org/10.4155/fmc-2021-0275] [PMID: 35050719]
[7]
Kumar, S.G.; Adithan, C.; Harish, B.N.; Roy, G.; Malini, A.; Sujatha, S. Antimicrobial resistance in India: A review. J. Nat. Sci. Biol. Med., 2013, 4(2), 286-291.
[http://dx.doi.org/10.4103/0976-9668.116970] [PMID: 24082718]
[8]
Kaur, P.; Chawla, A. 1,2,4-triazole: A review of pharmacological activities. Int. Res. J. Pharm., 2017, 8(7), 10-29.
[http://dx.doi.org/10.7897/2230-8407.087112]
[9]
Faisal, M.; Saeed, A.; Hussain, S.; Dar, P.; Larik, F.A. Recent developments in synthetic chemistry and biological activities of pyrazole derivatives. J. Chem. Sci., 2019, 131(8), 70.
[http://dx.doi.org/10.1007/s12039-019-1646-1]
[10]
Kaur, P.; Arora, V.; Kharb, R. Pyrazole as an anti-inflammatory scaffold. Int. J. Health Sci., 2022, 6(S2), 8281-8289.
[11]
Bekhit, A.A.; Hymete, A.; El-Din, A.; Bekhit, A.; Damtew, A.; Aboul-Enein, H.Y. Pyrazoles as promising scaffold for the synthesis of anti-inflammatory and/or antimicrobial agent: A review. Mini Rev. Med. Chem., 2010, 10(11), 1014-1033.
[http://dx.doi.org/10.2174/1389557511009011014] [PMID: 20540709]
[12]
Muhammad, Z.A.; Alshehrei, F.; Zayed, M.E.M.; Farghaly, T.A.; Abdallah, M.A. Synthesis of novel bis-pyrazole derivatives as antimicrobial agents. Mini Rev. Med. Chem., 2019, 19(15), 1276-1290.
[http://dx.doi.org/10.2174/1389557519666190313095545] [PMID: 30864524]
[13]
Alam, M.J.; Alam, O.; Alam, P.; Naim, M.J. A review on pyrazole chemical entity and biological activity. Int. J. Pharm. Sci. Res., 2015, 12(6), 1433-1442.
[14]
Ansari, A.; Ali, A.; Asif, M.; Shamsuzzaman, S. Biologically active pyrazole derivatives. New J. Chem., 2017, 41(1), 16-41.
[http://dx.doi.org/10.1039/C6NJ03181A]
[15]
Schmitt, D.C.; Taylor, A.P.; Flick, A.C.; Kyne, R.E., Jr Synthesis of pyrazoles from 1,3-diols via hydrogen transfer catalysis. Org. Lett., 2015, 17(6), 1405-1408.
[http://dx.doi.org/10.1021/acs.orglett.5b00266] [PMID: 25719568]
[16]
Zhang, Y.; Liu, J.; Jia, X. Phosphine-free [3+2] cycloaddition of propargylamines with dialkyl azodicarboxylates: An efficient access to pyrazole backbone. Synth, 2018, 50(17), 3499-3505.
[17]
Panda, N.; Jena, A.K. Fe-catalyzed one-pot synthesis of 1,3-Di and 1,3,5-trisubstituted pyrazoles from hydrazones and vicinal diols. J. Org. Chem., 2012, 77(20), 9401-9406.
[18]
Zhang, X.; Kang, J.; Niu, P.; Wu, J.; Yu, W.; Chang, J. I2-mediated oxidative C-N bond formation for metal-free one-pot synthesis of di-, tri-, and tetrasubstituted pyrazoles from αβ-unsaturated aldehydes/ketones and hydrazines. J. Org. Chem., 2014, 79(21), 10170-10178.
[http://dx.doi.org/10.1021/jo501844x] [PMID: 25279429]
[19]
Vilotijevic, I.; Drikermann, D.; Kerndl, V.; Görls, H. Intramolecular cyclization of vinyldiazoacetates as a versatile route to substituted pyrazoles. Synlett, 2020, 31(12), 1158-1162.
[http://dx.doi.org/10.1055/s-0040-1707111]
[20]
Wang, H.; Sun, X.; Zhang, S.; Liu, G.; Wang, C.; Zhu, L.; Zhang, H. Efficient copper-catalyzed synthesis of substituted pyrazoles at room temperature. Synlett, 2018, 29(20), 2689-2692.
[http://dx.doi.org/10.1055/s-0037-1610330]
[21]
Fan, X.W.; Lei, T.; Zhou, C.; Meng, Q.Y.; Chen, B.; Tung, C.H.; Wu, L.Z. Radical addition of hydrazones by α-bromo ketones to prepare 1,3,5-trisubstituted pyrazoles via visible light catalysis. J. Org. Chem., 2016, 81(16), 7127-7133.
[http://dx.doi.org/10.1021/acs.joc.6b00992] [PMID: 27362866]
[22]
Kumar, S.V.; Yadav, S.K.; Raghava, B.; Saraiah, B.; Ila, H.; Rangappa, K.S.; Hazra, A. Cyclocondensation of arylhydrazines with 1,3-bis(het)arylmonothio-1,3-diketones and 1,3-bis(het)aryl-3-(methylthio)-2-propenones: Synthesis of 1-Aryl-3,5-bis(het)arylpyrazoles with complementary regioselectivity. J. Org. Chem., 2013, 78(10), 4960-4973.
[http://dx.doi.org/10.1021/jo400599e] [PMID: 23607788]
[23]
Matsuzaki, H.; Takeda, N.; Yasui, M.; Ito, Y.; Konishi, K.; Ueda, M. Synthesis of pyrazoles utilizing the ambiphilic reactivity of hydrazones. Org. Lett., 2020, 22(23), 9249-9252.
[http://dx.doi.org/10.1021/acs.orglett.0c03465] [PMID: 33196204]
[24]
Faria, J.V.; Vegi, P.F.; Miguita, A.G.C.; dos Santos, M.S.; Boechat, N.; Bernardino, A.M.R. Recently reported biological activities of pyrazole compounds. Bioorg. Med. Chem., 2017, 25(21), 5891-5903.
[http://dx.doi.org/10.1016/j.bmc.2017.09.035] [PMID: 28988624]
[25]
Brogi, S.; Ramalho, T.C.; Kuca, K.; Medina-Franco, J.L.; Valko, M. In silico methods for drug design and discovery. Front Chem., 2020, 8, 612.
[http://dx.doi.org/10.3389/fchem.2020.00612] [PMID: 32850641]
[26]
Abdulfatai, U.; Uzairu, A.; Uba, S. Quantitative structure-activity relationship and molecular docking studies of a series of quinazolinonyl analogues as inhibitors of gamma amino butyric acid aminotransferase. J. Adv. Res., 2017, 8(1), 33-43.
[http://dx.doi.org/10.1016/j.jare.2016.10.004] [PMID: 27942417]
[27]
Hou, T.; Xu, X. Recent development and application of virtual screening in drug discovery: An overview. Curr. Pharm. Des., 2004, 10(9), 1011-1033.
[http://dx.doi.org/10.2174/1381612043452721] [PMID: 15078130]
[28]
El-Assaly, S.A.; Ismail, A.E.H.A.; Bary, H.A.; Abouelenein, M.G. Synthesis, molecular docking studies, and antimicrobial evaluation of pyrano[2, 3-c]pyrazole derivatives. Current Chemistry Letters, 2021, 10(3), 309-328.
[http://dx.doi.org/10.5267/j.ccl.2021.3.003]
[29]
Kaddouri, Y.; Bouchal, B.; Abrigach, F.; Elkodadi, M.; Bellaoui, M. Synthesis, molecular docking, MEP and SAR analysis, ADME-Tox predictions, and antimicrobial evaluation of novel mono and tetra-alkylated pyrazole and triazole ligands. J. Chem., 2021, 2021, 1-11.
[30]
Punia, S.; Verma, V.; Kumar, D.; Kumar, A.; Deswal, L. Facile synthesis, antimicrobial evaluation and molecular docking studies of pyrazole-imidazole-triazole hybrids. J. Mol. Struct., 2021, 1223, 129216.
[http://dx.doi.org/10.1016/j.molstruc.2020.129216]
[31]
Desai, N.C.; Joshi, S.B.; Khedkar, V.M. Synthesis, antimicrobial activity and molecular docking of pyrazole bearing the benzodiazepine moiety. Anal. Chem. Lett., 2020, 10(3), 307-320.
[http://dx.doi.org/10.1080/22297928.2020.1785325]
[32]
Desai, N.C.; Vaja, D.V.; Jadeja, K.A.; Joshi, S.B.; Khedkar, V.M. Synthesis, biological evaluation and molecular docking study of pyrazole, pyrazoline clubbed pyridine as potential antimicrobial agents. Antiinfect. Agents, 2020, 18(3), 306-314.
[http://dx.doi.org/10.2174/2211352517666190627144315]
[33]
Elkanzi, N.A.A.; Hrichi, H.; Bakr, R.B.; Hendawy, O.; Alruwaili, M.M.; Alruwaili, E.D.; Almamtrfi, R.W.; Alsharary, H.K. Synthesis, in vitro evaluation and molecular docking of new pyrazole derivatives bearing 1,5,10,10a-tetrahydrobenzo[g]quinoline-3-carbon-itrile moiety as potent antibacterial agents. J. Indian Chem. Soc., 2021, 18(4), 977-991.
[http://dx.doi.org/10.1007/s13738-020-02086-8]
[34]
Emami, L.; Zamani, L.; Sabet, R.; Zomorodian, K.; Rezaei, Z.; Faghih, Z.; Shahbazi, Y.; Khabnadideh, S. Molecular docking and antimicrobial evaluation of some novel pyrano[2,3-C] pyrazole derivatives. TIPS, 2020, 6(2), 113-120.
[35]
Fahim, A.M.; Farag, A.M. Synthesis, antimicrobial evaluation, molecular docking and theoretical calculations of novel pyrazolo[1,5-a]pyrimidine derivatives. J. Mol. Struct., 2020, 1199, 127025.
[http://dx.doi.org/10.1016/j.molstruc.2019.127025]
[36]
He, L.L.; Qi, Q.; Wang, X.; Li, Y.; Zhu, Y.; Wang, X.F.; Xu, L. Synthesis of two novel pyrazolo[1,5-a]pyrimidine compounds with antibacterial activity and biophysical insights into their interactions with plasma protein. Bioorg. Chem., 2020, 99(3), 103833.
[http://dx.doi.org/10.1016/j.bioorg.2020.103833] [PMID: 32305694]
[37]
Huang, Y.; Hu, H.; Yan, R.; Lin, L.; Song, M.; Yao, X. Synthesis and evaluation of antimicrobial and anticancer activities of 3‐phenyl‐1‐phenylsulfonyl pyrazoles containing an aminoguanidine moiety. Arch. Pharm., 2021, 354(2), 2000165.
[http://dx.doi.org/10.1002/ardp.202000165] [PMID: 33047391]
[38]
Khumar, A.B.S.; Kumar, K.N.; Raja, C.; Ezhilarasi, M.R. In vitro anticancer activity, antimicrobial and in silico studies of naphthyl pyrazole analogues. Rasayan J. Chem., 2020, 13(2), 1199-1214.
[http://dx.doi.org/10.31788/RJC.2020.1325495]
[39]
Song, M.; Liu, B.; Yu, S.; He, S.; Liang, Y.; Li, S.; Chen, Q.; Deng, X. New hydrazone derivatives of pyrazole-4-carboxaldehydes exhibited anti-inflammatory properties. Lett. Drug Des. Discov., 2020, 17(4), 502-511.
[http://dx.doi.org/10.2174/1570180816666190731113441]
[40]
Moustafa, A.H.; Ahmed, D.H.; El-Wassimy, M.T.M.; Mohamed, M.F.A. Synthesis, antimicrobial studies, and molecular docking of some new dihydro-1,3,4-thiadiazole and pyrazole derivatives derived from dithiocarbazates. Synth. Commun., 2021, 51(4), 570-584.
[http://dx.doi.org/10.1080/00397911.2020.1843179]
[41]
Nayak, S.G.; Poojary, B. Design, synthesis, in silico docking studies, and antibacterial activity of some thiadiazines and 1,2,4-triazole-3-thiones bearing pyrazole moiety. Russ. J. Bioorganic Chem., 2020, 46(1), 97-106.
[http://dx.doi.org/10.1134/S1068162020010069]
[42]
Othman, I.M.M.; Gad-Elkareem, M.A.M.; Amr, A.E.G.E.; Al-Omar, M.A.; Nossier, E.S.; Elsayed, E.A. Novel heterocyclic hybrids of pyrazole targeting dihydrofolate reductase: Design, biological evaluation and in silico studies. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 1491-1502.
[http://dx.doi.org/10.1080/14756366.2020.1791842] [PMID: 32668994]
[43]
Shetty, P.R.; Shivaraja, G.; Krishnaswamy, G.; Pruthviraj, K.; Mohan, V.C.; Sreenivasa, S. Pyrazole schiff bases: Synthesis, characterization, biological screening, in silico ADME and molecular docking studies. Indian J. Heterocycl. Chem., 2020, 30(2), 123-130.
[44]
Taresh, B.H.; Abdula, A.M.; Mohammed, M.T.; Baqer, S.M.; Khalil, M.A.A.; Rasheed, A.H. Novel 3,5-diaryl-4,5-dihydro-1h-pyrazole derivatives: Synthesis, antioxidant, antimicrobial and docking study against glucosamine-6-phosphate synthase. J. Chem., 2020, 2020(8), 1-10.
[45]
Abid, S.E.; Abdula, A.M.; Al Marjani, M.F.; Abdulhameed, Q.M. Synthesis, antimicrobial, antioxidant and docking study of some novel 3,5- disubstituted- 4,5- dihydro- 1H- pyrazoles incorporating imine moiety. Egypt. J. Chem., 2019, 62(4), 1139-1149.
[46]
Chu, M.J.; Wang, W.; Ren, Z.L.; Liu, H.; Cheng, X.; Mo, K.; Wang, L.; Tang, F.; Lv, X.H. Discovery of novel triazole-containing pyrazole ester derivatives as potential antibacterial agents. Molecules, 2019, 24(7), 1311.
[http://dx.doi.org/10.3390/molecules24071311] [PMID: 30987179]
[47]
Ebenezer, O.; Awolade, P.; Koorbanally, N.; Singh, P. New library of pyrazole-imidazo[1,2‐α]pyridine molecular conjugates: Synthesis, antibacterial activity and molecular docking studies. Chem. Biol. Drug Des., 2020, 95(1), 162-173.
[http://dx.doi.org/10.1111/cbdd.13632] [PMID: 31580533]
[48]
Konwar, M.; Phukan, P.; Chaliha, A.K.; Buragohain, A.K.; Damarla, K.; Gogoi, D.; Kumar, A.; Sarma, D. An unexplored lewis acidic catalytic system for synthesis of pyrazole and its biaryls derivatives with antimicrobial activities through cycloaddition‐iodination‐suzuki reaction. ChemistrySelect, 2019, 4(35), 10236-10245.
[http://dx.doi.org/10.1002/slct.201902266]
[49]
Sanad, S.M.H.; Hanna, D.H.; Mekky, A.E.M. Regioselective synthesis of novel antibacterial pyrazole-benzofuran hybrids: 2D NMR spectroscopy studies and molecular docking. J. Mol. Struct., 2019, 1188, 214-226.
[http://dx.doi.org/10.1016/j.molstruc.2019.03.088]
[50]
Shubhangi, K.N.; Kumar, N.; Kanagaraj, R.; Lal, K.; Paul, A.K. Modeling molecular interactions of propounded pyrazole based drug candidates against bacterial DNA gyrase: Validation by syntheses and biological studies. J. Mol. Struct., 2019, 1195, 435-450.
[http://dx.doi.org/10.1016/j.molstruc.2019.05.125]
[51]
Abrigach, F.; Rokni, Y.; Takfaoui, A.; Khoutoul, M.; Doucet, H.; Asehraou, A.; Touzani, R. In vitro screening, homology modeling and molecular docking studies of some pyrazole and imidazole derivatives. Biomed. Pharmacother., 2018, 103(3), 653-661.
[http://dx.doi.org/10.1016/j.biopha.2018.04.061] [PMID: 29679907]
[52]
Barakat, A.; Al-Majid, A.M.; Al-Qahtany, B.M.; Ali, M.; Teleb, M.; Al-Agamy, M.H.; Naz, S.; Ul-Haq, Z. Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures. Chem. Cent. J., 2018, 12(1), 29.
[http://dx.doi.org/10.1186/s13065-018-0399-0] [PMID: 29541952]
[53]
Flefel, E.M.; El-Sofany, W.I.; El-Shahat, M.; Naqvi, A.; Assirey, E. Synthesis, molecular docking and in vitro screening of some newly synthesized triazolopyridine, pyridotriazine and pyridine-pyrazole hybrid derivatives. Molecules, 2018, 23(10), 2548.
[http://dx.doi.org/10.3390/molecules23102548] [PMID: 30301217]
[54]
Gondru, R.; Sirisha, K.; Raj, S.; Gunda, S.K.; Kumar, C.G.; Pasupuleti, M.; Bavantula, R. Design, synthesis, in vitro evaluation and docking studies of pyrazole-thiazole hybrids as antimicrobial and antibiofilm agents. ChemistrySelect, 2018, 3(28), 8270-8276.
[http://dx.doi.org/10.1002/slct.201801391]
[55]
Hassan, G.S.; Abdel Rahman, D.E.; Abdelmajeed, E.A.; Refaey, R.H.; Alaraby Salem, M.; Nissan, Y.M. New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES. Eur. J. Med. Chem., 2019, 171, 332-342.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.052] [PMID: 30928706]
[56]
Khumar, A.B.S.; Ezhilarasi, M.R.; Prabha, B. Molecular docking study of novel synthesized pyrazole derivatives and their antibacterial activity. Asian J. Chem., 2018, 30(4), 741-746.
[http://dx.doi.org/10.14233/ajchem.2018.20913]
[57]
Shingare, R.M.; Patil, Y.S.; Sangshetti, J.N.; Damale, M.G.; Rajani, D.P.; Madje, B.R. Synthesis, antimicrobial evaluation and docking study of some pyrazole bearing [1, 2,4]triazolo[3, 4-b][1, 3,4]thiadiazole derivatives. ChemistrySelect, 2018, 3(14), 3899-3903.
[http://dx.doi.org/10.1002/slct.201800373]
[58]
Vekariya, M.K.; Vekariya, R.H.; Patel, K.D.; Raval, N.P.; Shah, P.U.; Rajani, D.P.; Shah, N.K. Pyrimidine-pyrazole hybrids as morpholinopyrimidine-based pyrazole carboxamides: Synthesis, characterisation, docking, ADMET study and biological evaluation. ChemistrySelect, 2018, 3(24), 6998-7008.
[http://dx.doi.org/10.1002/slct.201801011]
[59]
Banuppriya, G.; Sribalan, R.; Padmini, V. Evaluation of antioxidant, anti-inflammatory, antibacterial activity and in silico molecular docking study of pyrazole curcumin bisacetamide analogs. ChemistrySelect, 2017, 2(28), 9168-9173.
[http://dx.doi.org/10.1002/slct.201701533]
[60]
Gurunanjappa, P.; Kameshwar, V.H.; Kariyappa, A.K. Bioactive formylpyrazole analogues: Synthesis, antimicrobial, antioxidant and molecular docking studies. Asian J. Chem., 2017, 29(7), 1549-1554.
[http://dx.doi.org/10.14233/ajchem.2017.20562]
[61]
Ismail, A.H.; Abdula, A.M.; Taha, M.M.; Al-Bayati, R. 1,3,5-trisubstituted-1H-pyrazole derivatives as new antimicrobial agents: Synthesis, characterization and docking study. Int. J. Chem. Sci., 2017, 15(2), 8.
[62]
Khan, S.A.; Asiri, A.M.; Rahman, R.M.; Elroby, S.A.; Aqlan, F.M.S.; Wani, M.Y.; Sharma, K. Multistep synthesis of fluorine-substituted pyrazolopyrimidine derivatives with higher antibacterial efficacy based on in vitro molecular docking and density functional theory. J. Heterocycl. Chem., 2017, 54(6), 3099-3107.
[http://dx.doi.org/10.1002/jhet.2923]
[63]
Bhat, M.A.; Ahmed, A.F.; Wen, Z.H.; Al-Omar, M.A.; Abdel-Aziz, H.A. Synthesis, anti-inflammatory and neuroprotective activity of pyrazole and pyrazolo[3,4-d]pyridazine bearing 3,4,5-trimethoxyphenyl. Med. Chem. Res., 2017, 26(7), 1557-1566.
[http://dx.doi.org/10.1007/s00044-017-1870-5]
[64]
Chougala, B.M.; Samundeeswari, S.; Holiyachi, M.; Shastri, L.A.; Dodamani, S.; Jalalpure, S.; Dixit, S.R.; Joshi, S.D.; Sunagar, V.A. Synthesis, characterization and molecular docking studies of substituted 4-coumarinylpyrano[2,3-c]pyrazole derivatives as potent antibacterial and anti-inflammatory agents. Eur. J. Med. Chem., 2017, 125, 101-116.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.021] [PMID: 27657808]
[65]
Elshaier, Y.; Barakat, A.; Al-Qahtany, B.; Al-Majid, A.; Al-Agamy, M. Synthesis of pyrazole-thiobarbituric acid derivatives: Antimicrobial activity and docking studies. Molecules, 2016, 21(10), 1337.
[http://dx.doi.org/10.3390/molecules21101337] [PMID: 27735850]

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