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Current Microwave Chemistry

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ISSN (Print): 2213-3356
ISSN (Online): 2213-3364

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Research Article

Molecular Docking, Microwave-Assisted Synthesis, Characterization and Pharmacological Evaluation of 2,4,5-trisubstituted Imidazole’s

Author(s): Tanvi Goel, Deepali Bansode*, Raihan Arikkattel Abdu and Sanal Dev

Volume 10, Issue 1, 2023

Published on: 15 June, 2023

Page: [43 - 52] Pages: 10

DOI: 10.2174/2213335610666230420085314

Price: $65

Abstract

Introduction: Nitrogen containing heterocycles such as azoles have gained popularity in medicinal chemistry research due to their versatile pharmacological activities. Imidazole’s are one such class of adaptable compounds. The aim of the study was to explore pharmacological activities of 2,4,5- trisubstituted imidazole’s and also to develop a novel method of synthesis using microwave chemistry.

Methods: In the present study, the in-silico studies of 2,4,5-trisubstituted imidazole’s was carried out to predict their anti-leishmanial as well as COX-2 inhibitory activity. Although, the results are not satisfactory for the anti-leishmanial activity, the molecules showed comparable docking scores with standard celecoxib for the COX-2 inhibitory activity. Later, the microwave-assisted green synthesis of trisubstituted imidazole’s was attempted using green catalyst and solvent, molecular iodine and ethanol respectively. The synthesised derivatives (TG-1-4) were purified and characterised.

Results: The derivatives were subjected to in-vitro COX-2 inhibitory assay, which showed good results. The molecules under study showed exemplary results against COX-2 PDB in molecular docking studies. A novel microwave-irradiation method was developed for the synthesis and also the in-vivo studies carried out for testing COX-2 inhibition was fruitful.

Conclusion: In conclusion, the selected derivatives can be further studied in-vivo to develop new COX-2 inhibitors.

Keywords: Molecular docking, microwave-assisted synthesis, green chemistry, anti-leishmanial, COX-2 inhibition, pharmacological evaluation.

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[1]
Iradyan, M.A.; Aivazyan, A.K.; Mirzoyan, V.S.; Stepanyan, G.M.; Arsenyan, F.G.; Garibdzhanyan, B.T.; Paronikyan, G.M.; Sarkisyan, T.P. Imidazole derivatives. Synthesis and biological activity of derivatives of 4-nitro-5-thioimidazole. Pharm. Chem. J., 1988, 22(4), 287-292.
[http://dx.doi.org/10.1007/BF00768245]
[2]
Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K.K.; Jonnalagadda, S.B. A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules, 2020, 25(8), 1909.
[http://dx.doi.org/10.3390/molecules25081909] [PMID: 32326131]
[3]
Majumder, A.; Gupta, R.; Jain, A. Microwave-assisted synthesis of nitrogen-containing heterocycles. Green Chem. Lett. Rev., 2013, 6(2), 151-182.
[http://dx.doi.org/10.1080/17518253.2012.733032]
[4]
Sharma, A.; Appukkuttan, P.; Van der Eycken, E. Microwave-assisted synthesis of medium-sized heterocycles. Chem. Commun. (Camb.), 2012, 48(11), 1623-1637.
[http://dx.doi.org/10.1039/C1CC15238F] [PMID: 22031184]
[5]
Roberts, B.A.; Strauss, C.R. Toward rapid, “green”, predictable microwave-assisted synthesis. Acc. Chem. Res., 2005, 38(8), 653-661.
[http://dx.doi.org/10.1021/ar040278m] [PMID: 16104688]
[6]
Nüchter, M.; Ondruschka, B.; Bonrath, W.; Gum, A. Microwave assisted synthesis-A critical technology overview. Green Chem., 2004, 6(3), 128-141.
[http://dx.doi.org/10.1039/B310502D]
[7]
Hayes, B.; Hayes, B.L. Recent advances in microwave-assisted synthesis. Aldrichim Acta, 2015, 37(2), 66-77.
[8]
Bhargava, P.; Singh, R. Developments in diagnosis and antileishmanial drugs. Interdiscip. Perspect. Infect. Dis., 2012, 2012, 1-13.
[http://dx.doi.org/10.1155/2012/626838] [PMID: 23118748]
[9]
Bhandari, K.; Srinivas, N.; Marrapu, V.K.; Verma, A.; Srivastava, S.; Gupta, S. Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents. Bioorg. Med. Chem. Lett., 2010, 20(1), 291-293.
[http://dx.doi.org/10.1016/j.bmcl.2009.10.117] [PMID: 19913413]
[10]
Razzaghi-Asl, N.; Sepehri, S.; Ebadi, A.; Karami, P.; Nejatkhah, N.; Johari-Ahar, M. Insights into the current status of privileged N-heterocycles as antileishmanial agents. Mol. Divers., 2020, 24(2), 525-569.
[http://dx.doi.org/10.1007/s11030-019-09953-4] [PMID: 31028558]
[11]
Le Pape, P. Development of new antileishmanial drugs-current knowledge and future prospects. J. Enzyme Inhib. Med. Chem., 2008, 23(5), 708-718.
[http://dx.doi.org/10.1080/14756360802208137] [PMID: 18671165]
[12]
Rajasekaran, R.; Chen, Y.P.P. Potential therapeutic targets and the role of technology in developing novel antileishmanial drugs. Drug Discov. Today, 2015, 20(8), 958-968.
[http://dx.doi.org/10.1016/j.drudis.2015.04.006] [PMID: 25936844]
[13]
Ramey, D.R.; Watson, D.J.; Yu, C.; Bolognese, J.A.; Curtis, S.P.; Reicin, A.S. The incidence of upper gastrointestinal adverse events in clinical trials of etoricoxib vs. non-selective NSAIDs: An updated combined analysis. Curr. Med. Res. Opin., 2005, 21(5), 715-722.
[http://dx.doi.org/10.1185/030079905X43686] [PMID: 15974563]
[14]
Zhu, X.T.; Chen, L.; Lin, J.H. Selective COX-2 inhibitor versus non-selective COX-2 inhibitor for the prevention of heterotopic ossification after total hip arthroplasty. Medicine (Baltimore), 2018, 97(31), e11649.
[http://dx.doi.org/10.1097/MD.0000000000011649] [PMID: 30075549]
[15]
Little, D.; Jones, S.L.; Blikslager, A.T. Cyclooxygenase (COX) inhibitors and the intestine. J. Vet. Intern. Med., 2007, 21(3), 367-377.
[http://dx.doi.org/10.1111/j.1939-1676.2007.tb02978.x] [PMID: 17552439]
[16]
Mukherjee, D.; Nissen, S.E.; Topol, E.J. Risk of cardiovascular events associated with selective COX-2 inhibitors. ACC Curr. J. Rev., 2002, 11(1), 15.
[http://dx.doi.org/10.1016/S1062-1458(01)00545-1]
[17]
Mahajan, A.; Sharma, R. COX-2 selective nonsteroidal anti-inflammatory drugs: Current status. J. Assoc. Physicians India, 2005, 53, 200-204.
[PMID: 15926604]
[18]
Navidpour, L.; Shadnia, H.; Shafaroodi, H.; Amini, M.; Dehpour, A.R.; Shafiee, A. Design, synthesis, and biological evaluation of substituted 2-alkylthio-1,5-diarylimidazoles as selective COX-2 inhibitors. Bioorg. Med. Chem., 2007, 15(5), 1976-1982.
[http://dx.doi.org/10.1016/j.bmc.2006.12.041] [PMID: 17258905]
[19]
Hall, D.C., Jr; Ji, H.F. A search for medications to treat COVID-19 viain silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Med. Infect. Dis., 2020, 35, 101646.
[http://dx.doi.org/10.1016/j.tmaid.2020.101646] [PMID: 32294562]
[20]
Kishore Kumar, A.; Sunitha, V.; Shankar, B.; Ramesh, M.; Murali Krishna, T.; Jalapathi, P. Synthesis, biological evaluation, and molecular docking studies of novel 1,2,3-triazole derivatives as potent anti-inflammatory agents. Russ. J. Gen. Chem., 2016, 86(5), 1154-1162.
[http://dx.doi.org/10.1134/S1070363216050297]
[21]
Saccoliti, F.; Angiulli, G.; Pupo, G.; Pescatori, L.; Madia, V.N.; Messore, A.; Colotti, G.; Fiorillo, A.; Scipione, L.; Gramiccia, M.; Di Muccio, T.; Di Santo, R.; Costi, R.; Ilari, A. Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide derivatives. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 304-310.
[http://dx.doi.org/10.1080/14756366.2016.1250755] [PMID: 28098499]
[22]
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem., 2006, 49(21), 6177-6196.
[http://dx.doi.org/10.1021/jm051256o] [PMID: 17034125]
[23]
Jeong, G.S.; Kaipakasseri, S.; Lee, S.R.; Marraiki, N.; Batiha, G.E.S.; Dev, S.; Palakkathondi, A.; Kavully, F.S.; Gambacorta, N.; Nicolotti, O.; Mathew, B.; Kim, H. Selected 1,3‐benzodioxine‐containing chalcones as multipotent oxidase and acetylcholinesterase inhibitors. ChemMedChem, 2020, 15(23), 2257-2263.
[http://dx.doi.org/10.1002/cmdc.202000491] [PMID: 32924264]
[24]
Dev, S.; Dhaneshwar, S.R.; Mathew, B. Virtual combinatorial library design, synthesis and in vitro anticancer assessment of -2-amino-3-cyanopyridine derivatives. Comb. Chem. High Throughput Screen., 2018, 21(2), 138-148.
[http://dx.doi.org/10.2174/1386207321666180228113925] [PMID: 29493450]
[25]
Sangshetti, J.N.; Kokare, N.D.; Kotharkar, S.A.; Shinde, D.B. ZrOCl2·8H2O catalyzed one-pot synthesis of 2,4,5-triaryl-1H-imidazoles and substituted 1,4-di(4,5-diphenylimidazol-yl)benzene. Chin. Chem. Lett., 2008, 19(7), 762-766.
[http://dx.doi.org/10.1016/j.cclet.2008.05.007]
[26]
Joshi, R.S.; Mandhane, P.G.; Shaikh, M.U.; Kale, R.P.; Gill, C.H. Potassium dihydrogen phosphate catalyzed one-pot synthesis of 2,4,5-triaryl-1H-imidazoles. Chin. Chem. Lett., 2010, 21(4), 429-432.
[http://dx.doi.org/10.1016/j.cclet.2009.11.012]
[27]
Ghogare, R. Mandelic acid: an efficient and green organo-catalyst for synthesis of 2,4,5-trisubstituted Imidazoles under solvent free condition. Org. Commun., 2022, 15(1), 44-58.
[http://dx.doi.org/10.25135/acg.oc.118.22.01.2341]
[28]
Kidwai, M.; Mothsra, P.; Bansal, V.; Somvanshi, R.K.; Ethayathulla, A.S.; Dey, S.; Singh, T.P. One-pot synthesis of highly substituted imidazoles using molecular iodine: A versatile catalyst. J. Mol. Catal. Chem., 2007, 265(1-2), 177-182.
[http://dx.doi.org/10.1016/j.molcata.2006.10.009]

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