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Current Enzyme Inhibition

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ISSN (Print): 1573-4080
ISSN (Online): 1875-6662

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Research Article

Synthesis, In-silico and In-vitro Antimycobacterial Studies on Novel Benzofuran Derivatives

Author(s): Dnyaneshwar E. Shelke, Bapu R. Thorat*, Sanjay S. Dhabarde and Suraj N. Mali

Volume 19, Issue 1, 2023

Published on: 25 August, 2022

Page: [2 - 9] Pages: 8

DOI: 10.2174/1573408018666220802113450

Price: $65

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Abstract

Background: Benzofurans, interesting heterocyclic compounds, are available abundantly in nature and show a wider range of pharmacological activities. Moreover, in recent years this moiety has been found to have strong antituberculosis potential. Considering the importance of this moiety in the field of medicinal chemistry, we have synthesized a few benzofuran derivatives.

Methods: These derivatives were also characterized by standard spectroscopic methods. Synthesized compounds were observed for their anti-tuberculosis activity using microplate Alamar Blue assay (MABA) assay and found to have a minimum of 100 (μg/mL) of minimum inhibitory concentration (MIC) values. Moreover, our molecular docking analyses depicted strong inhibitory potential against a popular TB target, Decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1), a crucial enzyme for cell wall synthesis.

Results: Compound 9e was found to have a strong binding energy score of -148.47 kcal/mol against the selected targets (PDB id: 6HEZ).

Conclusion: All compounds were also found to possess drug-likeness characteristics when checked with Lipinski's filter.

Keywords: Synthesis, benzofurans, heterocycle, DprE1, drug-likeness, in- vitro antimycobacterial studies.

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[1]
Lv, K.; Li, L.; Wang, B.; Liu, M.; Wang, B.; Shen, W.; Guo, H.; Lu, Y. Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives. Eur. J. Med. Chem., 2017, 137, 117-125.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.044] [PMID: 28577507]
[2]
Tuberculosis. Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis#
[3]
Kamal, M.; Shakya, A.K.; Jawaid, T. Benzofurans: A new profile of biological activities. Int. J. Med. Pharm. Sci., 2011, 1, 1-15.
[4]
Cottineau, B.; Toto, P.; Marot, C.; Pipaud, A.; Chenault, J. Synthesis and hypoglycemic evaluation of substituted pyrazole-4-carboxylic acids. Bioorg. Med. Chem. Lett., 2002, 12(16), 2105-2108.
[http://dx.doi.org/10.1016/S0960-894X(02)00380-3] [PMID: 12127514]
[5]
Xie, Y.S.; Kumar, D.; Bodduri, V.D.V.; Tarani, P.S.; Zhao, B.X.; Miao, J.Y.; Jang, K.; Shin, D.S. Microwave-assisted parallel synthesis of benzofuran-2-carboxamide derivatives bearing anti-inflammatory, analgesic and antipyretic agents. Tetrahedron Lett., 2014, 55(17), 2796-2800.
[http://dx.doi.org/10.1016/j.tetlet.2014.02.116]
[6]
Thévenin, M.; Thoret, S.; Grellier, P.; Dubois, J. Synthesis of polysubstituted benzofuran derivatives as novel inhibitors of parasitic growth. Bioorg. Med. Chem., 2013, 21(17), 4885-4892.
[http://dx.doi.org/10.1016/j.bmc.2013.07.002] [PMID: 23902828]
[7]
Koca, M.; Servi, S.; Kirilmis, C.; Ahmedzade, M.; Kazaz, C.; Ozbek, B.; Otük, G. Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 1. Synthesis and antimicrobial activity of (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives. Eur. J. Med. Chem., 2005, 40(12), 1351-1358.
[http://dx.doi.org/10.1016/j.ejmech.2005.07.004] [PMID: 16129517]
[8]
Xie, F.; Zhu, H.; Zhang, H.; Lang, Q.; Tang, L.; Huang, Q.; Yu, L. In vitro and in vivo characterization of a benzofuran derivative, a potential anticancer agent, as a novel Aurora B kinase inhibitor. Eur. J. Med. Chem., 2015, 89, 310-319.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.044] [PMID: 25462247]
[9]
Oter, O.; Ertekin, K.; Kirilmis, C.; Koca, M.; Ahmedzade, M. Characterization of a newly synthesized fluorescent benzofuran derivative and usage as a selective fiber optic sensor for Fe(III). Sens. Actuators B Chem., 2007, 122(2), 450-456.
[http://dx.doi.org/10.1016/j.snb.2006.06.010]
[10]
Karatas, F.; Koca, M.; Kara, H.; Servi, S. Synthesis and oxidant properties of novel (5-bromobenzofuran-2-yl)(3-methyl-3-mesitylcyclobutyl)ketonethiosemicarbazone. Eur. J. Med. Chem., 2006, 41(5), 664-669.
[http://dx.doi.org/10.1016/j.ejmech.2006.01.003] [PMID: 16527373]
[11]
Thorat, B.R.; Mali, S.N.; Rani, D.; Yamgar, R.S. Synthesis, in silico and in vitro analysis of hydrazones as potential antituberculosis agents. Curr. Computeraided Drug Des., 2021, 17(2), 294-306.
[http://dx.doi.org/10.2174/1573409916666200302120942] [PMID: 32141422]
[12]
Desale, V.J.; Mali, S.N.; Thorat, B.R.; Yamgar, R.S. Synthesis, admetSAR predictions, DPPH Radical scavenging activity, and potent anti-mycobacterial studies of hydrazones of substituted 4-(anilino methyl) benzohydrazides (Part 2). Curr. Computeraided Drug Des., 2021, 17(4), 493-503.
[http://dx.doi.org/10.2174/1573409916666200615141047] [PMID: 32538732]
[13]
Mali, S.N.; Pandey, A. Multiple QSAR and molecular modelling for identification of potent human adenovirus inhibitors. J. Indian Chem. Soc., 2021, 98(6), 100082.
[http://dx.doi.org/10.1016/j.jics.2021.100082]
[14]
Desale, V.J.; Mali, S.N.; Chaudhari, H.K.; Mali, M.C.; Thorat, B.R.; Yamgar, R.S. Synthesis and anti-mycobacterium study on halo-substituted 2-aryl oxyacetohydrazones. Curr. Computeraided Drug Des., 2020, 16(5), 618-628.
[http://dx.doi.org/10.2174/1573409915666191018120611] [PMID: 31648645]
[15]
Anuse, D.G.; Mali, S.N.; Thorat, B.R.; Yamgar, R.S.; Chaudhari, H.K. Synthesis, SAR, in silico appraisal and anti-microbial study of substituted 2-aminobenzothiazoles derivatives. Curr. Computeraided Drug Des., 2020, 16(6), 802-813.
[http://dx.doi.org/10.2174/1573409915666191210125647] [PMID: 31820704]
[16]
Thorat, B.R.; Rani, D.; Yamgar, R.S.; Mali, S.N. Synthesis, spectroscopic, in vitro and computational analysis of hydrazones as potential antituberculosis agents: (Part-I). Comb. Chem. High Throughput Screen., 2020, 23(5), 392-401.
[http://dx.doi.org/10.2174/1386207323999200325125858] [PMID: 32209038]
[17]
Bapu, R. Wittig reaction approach for the synthesis of 7-methoxy-2-[4- alkyl/aryl]-l-benzofuran-5-carboxaldehyde. Heterocyclic Letter, 2013, 3(3), 385.
[18]
Mali, S.N.; Pandey, A. Balanced QSAR and molecular modeling to identify structural requirements of imidazopyridine analogues as anti-infective agents against trypanosomiases. J. Comput. Biophys. and Chem., 2021, 21(1), 83-114.
[19]
Neto, R.A.M.; Santos, C.B.R.; Henriques, S.V.C.; Machado, L.O.; Cruz, J.N.; da Silva, C.H.T.P.; Federico, L.B.; Oliveira, E.H.C.; de Souza, M.P.C.; da Silva, P.N.B.; Taft, C.A.; Ferreira, I.M.; Gomes, M.R.F. Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations. J. Biomol. Struct. Dyn., 2022, 40(5), 2204-2216.
[http://dx.doi.org/10.1080/07391102.2020.1839562]
[20]
Santana de Oliveira, M.; Pereira da Silva, V.M.; Cantão Freitas, L.; Gomes Silva, S.; Nevez Cruz, J.; de Aguiar Andrade, E.H. Extraction yield, chemical composition, preliminary toxicity of Bignonia nocturna (bignoniaceae) essential oil and in silico evaluation of the interaction. Chem. Biodivers., 2021, 18(4), e2000982.
[http://dx.doi.org/10.1002/cbdv.202000982] [PMID: 33587821]
[21]
Costa, E.B.; Silva, R.C.; Espejo-Román, J.M.; Neto, M.F.A.; Cruz, J.N.; Leite, F.H.A.; Silva, C.H.T.P.; Pinheiro, J.C.; Macêdo, W.J.C.; Santos, C.B.R. Chemometric methods in antimalarial drug design from 1,2,4,5-tetraoxanes analogues. SAR QSAR Environ. Res., 2020, 31(9), 677-695.
[http://dx.doi.org/10.1080/1062936X.2020.1803961] [PMID: 32854545]
[22]
Mali, S.N.; Pandey, A. Molecular modeling studies on 2, 4-disubstituted imidazopyridines as anti-malarials: Atom-based 3D-QSAR, molecular docking, virtual screening, in silico admet and theoretical analysis. J. Comput. Biophys. Chem., 2021, 20(03), 267-282.
[http://dx.doi.org/10.1142/S2737416521500125]
[23]
Manina, G.; Pasca, M.R.; Buroni, S.; De Rossi, E.; Riccardi, G. Decaprenylphosphoryl-β-D-ribose 2′-epimerase from Mycobacterium tuberculosis is a magic drug target. Curr. Med. Chem., 2010, 17(27), 3099-3108.
[http://dx.doi.org/10.2174/092986710791959693] [PMID: 20629622]
[24]
Crellin, P.K.; Brammananth, R.; Coppel, R.L. Decaprenylphosphoryl-β-D-ribose 2′-epimerase, the target of benzothiazinones and dinitrobenzamides, is an essential enzyme in Mycobacterium smegmatis. PLoS One, 2011, 6(2), e16869.
[http://dx.doi.org/10.1371/journal.pone.0016869] [PMID: 21346818]
[25]
Hsu, K.C.; Chen, Y.F.; Lin, S.R.; Yang, J.M. iGEMDOCK: A graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinformatics, 2011, 12(1)(Suppl. 1), S33.
[http://dx.doi.org/10.1186/1471-2105-12-S1-S33] [PMID: 21342564]
[26]
A structural view of biology. Available from: https://www.rcsb.org/
[27]
Brecik, M.; Centárová, I.; Mukherjee, R.; Kolly, G.S.; Huszár, S.; Bobovská, A.; Kilacsková, E.; Mokošová, V.; Svetlíková, Z.; Šarkan, M.; Neres, J.; Korduláková, J.; Cole, S.T.; Mikušová, K. DprE1 is a vulnerable tuberculosis drug target due to its cell wall localization. ACS Chem. Biol., 2015, 10(7), 1631-1636.
[http://dx.doi.org/10.1021/acschembio.5b00237] [PMID: 25906160]
[28]
Thorat, B.R.; Jagtap, R.; Thorat, V.B.; Mandewale, M.; Nagarsekar, A.; Yamgar, R.S. Synthesis, molecular docking and cytotoxic study of 7-methoxy-2-(3,4-dimethoxyphenyl)-1-benzofuran-5-carbaldehyde. Pharma Chem., 2015, 7(9), 130-144.
[29]
Collins, L.; Franzblau, S.G. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother., 1997, 41(5), 1004-1009.
[http://dx.doi.org/10.1128/AAC.41.5.1004] [PMID: 9145860]

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