Synthesis, Biological Evaluation and Molecular Docking Study of Pyrazole, Pyrazoline Clubbed Pyridine as Potential Antimicrobial Agents

Author(s): Nisheeth C. Desai*, Darshita V. Vaja, Krunalsinh A. Jadeja, Surbhi B. Joshi, Vijay M. Khedkar

Journal Name: Anti-Infective Agents
Formerly Anti-Infective Agents in Medicinal Chemistry

Volume 18 , Issue 3 , 2020


DOI : 10.2174/2211352517666190627144315

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Graphical Abstract:


Abstract:

Introduction: In continuation of our efforts to find new antimicrobials, herein we report the synthesis of various pyrazole, pyrazoline, and pyridine based novel bioactive heterocycles (3a-t).

Methods: Newly synthesized compounds were analysed for their antimicrobial activity. Compounds 3c, 3h, 3i, 3k, 3n, and 3q showed significant antimicrobial activity.

Results: Molecular docking study for the most active analogues against DNA gyrase subunit b (PDB ID: 1KZN) corroborated well with the observed antimicrobial potency exhibiting significant binding affinity.

Conslusion: Interpretation of the chemical structures reported in this paper was based on IR, 1H NMR, 13C NMR, and mass spectral data.

Keywords: Pyrazole, pyrazoline, pyridine, heterocycles, antimicrobial activity, molecular docking.

[1]
Frieri, M.; Kumar, K.; Boutin, A. Antibiotic resistance. J. Infect. Public Health, 2017, 10(4), 369-378.
[http://dx.doi.org/10.1016/j.jiph.2016.08.007] [PMID: 27616769]
[2]
Nayak, N.; Ramprasad, J.; Dalimba, U. New INH-pyrazole analogs: Design, synthesis and evaluation of antitubercular and antibacterial activity. Bioorg. Med. Chem. Lett., 2015, 25(23), 5540-5545.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.057] [PMID: 26520663]
[3]
Desai, N.C.; Vaja, D.V. Hybrid Approach for Synthesis and Antimicrobial Activity of Heterocyclic Compounds. Int Lett Chem Phys Astron, 2018, 77, 35-52.
[http://dx.doi.org/10.18052/www.scipress.com/ILCPA.77.35]
[4]
Amnerkar, N.D.; Bhusari, K.P. Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. Eur. J. Med. Chem., 2010, 45(1), 149-159.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.037] [PMID: 19853976]
[5]
Balbi; Anzaldi, M.; Maccio, C.; Aiello, C.; Mazzei, M.; Gangemi, R.; Castagnola, P.; Miele, M.; Rosano, C.; Viale, M. Synthesis and biological evaluation of novel pyrazole derivatives with anticancer activity. Eur. J. Med. Chem., 2011, 46, 5293-5309.
[http://dx.doi.org/10.1016/j.ejmech.2011.08.014]
[6]
el-Sabbagh, O.I.; Baraka, M.M.; Ibrahim, S.M.; Pannecouque, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; Rashad, A.A. Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur. J. Med. Chem., 2009, 44(9), 3746-3753.
[http://dx.doi.org/10.1016/j.ejmech.2009.03.038] [PMID: 19419804]
[7]
Padmaja, A.; Rajasekhar, C.; Muralikrishna, A.; Padmavathi, V. Synthesis and antioxidant activity of oxazolyl/thiazolylsulfonylmethyl pyrazoles and isoxazoles. Eur. J. Med. Chem., 2011, 46(10), 5034-5038.
[http://dx.doi.org/10.1016/j.ejmech.2011.08.010] [PMID: 21864949]
[8]
Gawad, N.M.; Hassan, G.S.; Georgey, H.H. Design and synthesis of some pyrazole derivatives of expected anti-inflammatory and analgesic activities. Med. Chem. Res., 2012, 21, 983-994.
[http://dx.doi.org/10.1007/s00044-011-9606-4]
[9]
Kaplancikli, Z.A.; Ozdemir, A.; Turan-Zitouni, G.; Altintop, M.D.; Can, O.D. New pyrazoline derivatives and their antidepressant activity. Eur. J. Med. Chem., 2010, 45(9), 4383-4387.
[http://dx.doi.org/10.1016/j.ejmech.2010.06.011] [PMID: 20587366]
[10]
Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids, 2015, 98, 80-91.
[http://dx.doi.org/10.1016/j.steroids.2015.03.001] [PMID: 25759119]
[11]
Jose, G.; Suresha Kumara, T.H.; Nagendrappa, G.; Sowmya, H.B.V.; Sriram, D.; Yogeeswari, P.; Sridevi, J.P.; Guru Row, T.N.; Hosamani, A.A.; Sujan Ganapathy, P.S.; Chandrika, N.; Narendra, L.V. Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives. Eur. J. Med. Chem., 2015, 89, 616-627.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.079] [PMID: 25462270]
[12]
Ghattas, A.E.A.G.; Khodairy, A.; Moustafa, H.M.; Hussein, B.R.M. New Heterocyclic Compounds Derived from 4,6-Diamino-3-cyano-2-methylthiopyridine and their Biological Activity. J. Heterocycl. Chem., 2017, 54, 879-888.
[http://dx.doi.org/10.1002/jhet.2649]
[13]
Prasanthi, G.; Prasad, K.V.; Bharathi, K. Synthesis, anticonvulsant activity and molecular properties prediction of dialkyl 1-(di(ethoxycarbonyl)methyl)-2,6-dimethyl-4-substituted-1,4-dihydropyridine-3,5-dicarboxylates. Eur. J. Med. Chem., 2014, 73, 97-104.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.001] [PMID: 24384550]
[14]
Desai, N.C.; Kotadiya, G.M. Facile Synthesis of Pyrazole Encompassing Pyridyl Oxadiazoles Using Conventional and Microwave Techniques. Curr. Org. Chem., 2014, 18, 2561-2570.
[http://dx.doi.org/10.2174/138527281819141028114856]
[15]
Shaharyar, M.; Abdullah, M.M.; Bakht, M.A.; Majeed, J. Pyrazoline bearing benzimidazoles: search for anticancer agent. Eur. J. Med. Chem., 2010, 45(1), 114-119.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.032] [PMID: 19883957]
[16]
Kumar, S. Meenakshi; Kumar, S.; Kumar, P. Synthesis and antimicrobial activity of some (3-phenyl-5-(1-phenyl-3-aryl-1H-pyrazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones: new derivatives of 1,3,5-trisubstituted pyrazolines. Med. Chem. Res., 2013, 22, 433-439.
[http://dx.doi.org/10.1007/s00044-012-0045-7]
[17]
Hannan, P.C. Guidelines and recommendations for antimicrobial minimum inhibitory concentration (MIC) testing against veterinary mycoplasma species. International Research Programme on Comparative Mycoplasmology. Vet. Res., 2000, 31(4), 373-395.
[http://dx.doi.org/10.1051/vetres:2000100] [PMID: 10958240]
[18]
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]
[19]
Halgren, T.A.; Murphy, R.B.; Friesner, R.A.; Beard, H.S.; Frye, L.L.; Pollard, W.T.; Banks, J.L. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem., 2004, 47(7), 1750-1759.
[http://dx.doi.org/10.1021/jm030644s] [PMID: 15027866]
[20]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[21]
RCSB protein Data Bank http://www.rcsb.org/pdb (Accessed March 18, 2019)


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Article Details

VOLUME: 18
ISSUE: 3
Year: 2020
Published on: 27 June, 2019
Page: [306 - 314]
Pages: 9
DOI: 10.2174/2211352517666190627144315

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