One-Pot Three-Component Synthesis and Molecular Docking of Some Novel 2-Thiazolyl Pyridines as Potent Antimicrobial Agents

Author(s): Fathy M. Abdelrazek, Sobhi M. Gomha*, Mohamed E.B. Shaaban, Kamal A. Rabee, Heba N. El-Shemy, Abanoub M. Abdallah, Peter Metz

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Thiazoles and pyridines are versatile synthetic scaffolds possessing wide spectrum of biological effects including potential antimicrobial activity.

Objective: In the efforts to develop suitable antimicrobia drugs, medicinal chemists have focused on thiazole derivatives. A novel series of 2-thiazolyl pyridines was prepared in a one-pot three-component reaction using 2-bromoacetyl pyridine as a starting precursor.

Method: Structure of the synthesized compounds was elucidated by spectral data (FT-IR, 1H NMR, 13C NMR, and mass) and elemental analyses. The prepared compounds were screened for their in vitro antimicrobial activity.

Results: The results revealed that compounds 4a,b,e-g and 12 showed promising activity. Molecular docking studies using MOE software were carried out for compounds 4a and 4b which exhibited potent activities indicated by the diameter zones (4a; 3.6, 4.0, 1.2 mm) (4b; 4.2, 3.5, 1.5 mm) and the binding affinities (4a; -5.7731, -5.3576, -4.6844 kcal mol-1) (4b; -5.9356, -2.8250, -5.3628 kcal mol-1) against Candida albicans, Bacillus subtilis and Escherichia coli, respectively.

Conclusion: This paper describes a facile and efficient MCR for synthesis of 2-thiazolyl pyridines from reaction of 2-bromoacetyl pyridine with different reagents. There was an agreement between the values of binding affinities and interactions and the data obtained from the practical antimicrobial screening of the tested compounds.

Keywords: 2-Bromoacetylpyridine, thiosemicarbazide, thiazoles, hydrazonoyl halides, antimicrobial activity, molecular docking studies.

Karegoudar, P.; Karthikeyan, M.S.; Prasad, D.J.; Mahalinga, M.; Holla, B.S.; Kumari, N.S. Synthesis of some novel 2,4-disubstituted thiazoles as possible antimicrobial agents. Eur. J. Med. Chem., 2008, 43, 261-267.
Cukurovali, A.; Yilmaz, I.; Gur, S.; Kazaz, C. Synthesis, antibacterial and antifungal activity of some new thiazolylhydrazone derivatives containing 3-substituted cyclobutane ring. Eur. J. Med. Chem., 2006, 41, 201-207.
Abdel-Wahab, B.F.; Abdel-Aziz, H.A.; Ahmed, E.M. Synthesis and antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-(benzofuran-2-yl)-4,5-dihydro- 5-aryl- 1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles. Eur. J. Med. Chem., 2009, 44, 2632-2635.
Shih, M.H.; Ying, K.F. Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives. Bioorg. Med. Chem., 2004, 12, 4633-4643.
Shiradkar, M.; Kumar, G.V.S.; Dasari, V.; Tatikonda, S.; Akula, K.C.; Shah, R. Clubbed triazoles: a novel approach to antitubercular drugs. Eur. J. Med. Chem., 2007, 42(6), 807-816.
Amin, K.M.; Rahman, A.D.E.; Al-Eryani, Y.A. Synthesis and preliminary evaluation of some substituted coumarins as anticonvulsant agents. Bioorg. Med. Chem., 2008, 16, 5377-5388.
Gomha, S.M.; Riyadh, S.M.; Abbas, I.M.; Bauomi, M.A. Synthetic utility of ethylidenethiosemicarbazide: synthesis and anticancer activity of 1,3-thiazines and thiazoles with imidazole moiety. Heterocycles, 2013, 87, 341-356.
Gomha, S.M.; Abdel-aziz, H.M.; Khalil, K.D. Synthesis and SAR study of the novel thiadiazole-imidazole derivatives as new anti-cancer agents. Chem. Pharm. Bull., 2016, 64, 1356-1363.
Gomha, S.M.; Edrees, M.M.; Altalbawy, F.M.A. Synthesis and characterization of some new bis-pyrazolyl-thiazoles incorporating the thiophene moiety as potent anti-tumor agents. Intl. J. Mol. Sci.,2016, 17, 1499(1-12).
Gomha, S.M.; Salah, T.A.; Abdelhamid, A.O. Synthesis, characterization and pharmaco- logical evaluation of some novel thiadiazoles and thiazoles incorporating pyrazole moiety as potent anticancer agents. Monatsh. Chem., 2015, 146, 149-158.
Abdalla, M.A.; Gomha, S.M.; Abdelaziz, M.; Serag, N. Synthesis and antiviral evaluation of some novel thiazoles and 1,3-thiazines substituted with pyrazole moiety against rabies virus. Turk. J. Chem., 2016, 40, 441-453.
Dawood, K.M.; Gawad, H.A.; Rageb, E.A.; Ellithey, M.; Mohamed, H.A. Synthesis, anticonvulsant, anti-inflammatory evaluation of some new benzotriazole and bezofuran-based heterocycle. Bioorg. Med. Chem., 2006, 14, 3672-3680.
Carter, J.S.; Kramer, S.; Talley, J.J.; Penning, T.; Collins, P.; Graneto, M.J.; Seibert, K.; Koboldt, C.; Masferrer, J.; Zweifel, B. Synthesis and activity of sulfonamide-substituted 4,5-diaryl thiazoles as selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett., 1999, 9, 1171-1174.
Zhu, L.P.; Ye, D.Y.; Tang, Y. Structure-based 3D-QSAR studies on thiazoles as 5-HT3 receptor antagonists. J. Mol. Model., 2007, 13, 121-131.
Clark, R.F.; Zhang, T.; Wang, X.; Wang, R.; Zhang, X.; Camp, H.S.; Beutel, B.A.; Sham, H.L.; Gu, Y.J. Phenoxy thiazole derivatives as potent and selective acetyl-CoA carboxylase 2 inhibitors: Modulation of isozyme selectivity by incorporation of phenyl ring substituents. Bioorg. Med. Chem. Lett., 2007, 17, 1961-1965.
Saravanan, G.; Alagarsamy, V.; Prakash, C.R.; Kumar, P.; Dinesh, T.; Selvam, P. Synthesis of novel thiazole derivatives as analgesic agents. Asian J. Res. Pharm. Sci., 2011, 1, 134-138.
Abdelrazek, F.M.; Metz, P.; Metwally, N.H.; El-Mahrouky, S.F. Synthesis and molluscicidal activity of new cinnoline and pyrano [2,3-c]pyrazole Derivatives. Arch. Pharm. Chem. life Sci.,2006, 339, 456-460.
Abdelrazek, F.M.; Metwally, N.H. Novel synthesis of N-arylpyrrole, pyrrolo[1,2-a] quinazoline, and pyrrolo[3,4-d]pyridazine derivatives. Synth. Commun., 2009, 39, 4088-4099.
Abdelrazek, F.M.; Kassab, N.A.; Metwally, N.H.; Sobhy, N.A. Synthesis of some novel pyridine and naphthyridine derivatives. Eur. J. Chem., 2010, 1, 368-372.
Gomha, S.M.; Abdelrazek, F.M.; Abdulla, M.M.J. Synthesis of new functionalised derivatives of [1,2,4]triazolo[4,3-a]pyrimidine and pyrimido[2,1-b][1,3,5]thiadiazine as aromatase inhibitors. Chem. Res., 2015, 39, 425-429.
Gomha, S.M.; Eldebss, T.M.A.; Abdulla, M.M.; Mayhoub, A.S. Diphenylpyrroles: Novel p53 activators. Eur. J. Med. Chem., 2014, 82, 472-479.
Gomha, S.M. A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]- 1,2,4-triazolo[4,5-a]pyrimidin-5-ones. Monatsh. Chem., 2009, 140, 213-220.
Badrey, M.G.; Gomha, S.M. 3-Amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5–dihydro -3H-chromeno[2,3-d]pyrimidine: An Effecient key precursor for novel synthesis of some interesting triazines and triazepines as potential anti-tumor agents. Molecules, 2012, 17, 11538-11553.
Abbas, I.M.; Gomha, S.M.; Elneairy, M.A.A.; Elaasser, M.M.; Mabrouk, B.K.A. Synthesis and characterisation of some novel fused thiazolo[3,2-a]pyrimidinones and pyrimido[2,1-b][1,3]-thiazinones. J. Chem. Res., 2015, 39, 719-723.
Abdelrazek, F.M.; Gomha, S.M.; Abdelrahman, A.H.; Metz, P.; Sayed, M.A. A Facile synthesis and drug design of some new heterocyclic compounds incorporating pyridine moiety and their antimicrobial evaluation; Lett. Drug Des. Disc, 2017.
Abdelrazek, F.M.; Gomha, S.M.; Metz, P.; Abdulla, M.M. Synthesis of some novel 1,4-phenylene-bis-thiazolyl derivatives and their anti-hypertensive α-blocking activity screening. J. Heterocycl. Chem., 2017, 54, 618-623.
Gomha, S.M.; Abdelrazek, F.M.; Abdelrahman, A.H.; Metz, P. Synthesis of some novel thiazole, thiadiazole and 1,4-phenelen-bis-thiazole derivatives as potent antitumor agent. Heterocycles, 2016, 92, 954-967.
Hossain, M.A.; Shah, M.D.; Sang, S.V.; Sakari, M. Chemical composition and antibacterial properties of the essential oil and crude extract of merremia borneesis. J. King Saud. Univ., 2012, 24, 243-249.
Molecular operating environment (MOE 2008.10), Chemical computing group inc., montreal, QC, Canada.
RCSB Protein Data Bank.
Mjambili, F.; Njoroge, M.; Naran, K.; De Kock, C.; Smith, P.J.; Mizrahi, V.; Warner, D.; Chibale, K. Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents. Bioorg. Med. Chem. Lett., 2014, 24, 560-564.
Mohammad, S.A.; Lijun, L.; Eok, L.Y.; Ung, L.D. Synthesis, Antibacterial Activity and Quantum-Chemical Studies of Novel
2-Arylidenehydrazinyl-4-arylthiazole Analogues. Chem. Pharm. Bull., 2011, 59, 568-573.
Shawali, A.S.; Gomha, S.M. A New Entry for Short and regioselective synthesis of [1,2,4]triazolo[4,3-b][1,2,4]-triazin-7(1H)-ones. Adv. Synth. Catal., 2000, 342, 599-604.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [527 - 538]
Pages: 12
DOI: 10.2174/1389557518666181019124104
Price: $65

Article Metrics

PDF: 27