Design, Synthesis, Evaluation of Antimicrobial Activity and Docking Studies of New Thiazole-based Chalcones

Author(s): Christophe Tratrat*, Michelyne Haroun, Iakovos Xenikakis, Konstantinos Liaras, Evangelia Tsolaki, Phaedra Eleftheriou, Anthi Petrou, Bandar Aldhubiab, Mahesh Attimarad, Katharigatta N. Venugopala, Sree Harsha, Heba S. Elsewedy, Athina Geronikaki*, Marina Soković

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 5 , 2019

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Graphical Abstract:


Background: Thiazole derivates as well as chalcones, are very important scaffold for medicinal chemistry. Literature survey revealed that they possess wide spectrum of biological activities among which are anti-inflammatory and antimicrobial.

Objectives: The current studies describe the synthesis and evaluation of antimicrobial activity of twenty eight novel thiazole-based chalcones.

Methods: The designed compounds were synthesized using classical methods of organic synthesis. The in vivo evaluation of antimicrobial activity was performed by microdilution method.

Results: All compounds have shown antibacterial properties better than that of ampicillin and in many cases better than streptomycin. As far as the antifungal activity is concerned, all compounds possess much higher activity than reference drugs bifonazole and ketoconazole. The most sensitive bacterial species was B. cereus (MIC 6.5-28.4 µmol × 10-2/mL and MBC 14.2-105.0 µmol × 10-2/mL) while the most resistant ones were L. monocytogenes (MIC 21.4-113.6 µmol × 10-2/mL) and E. coli (MIC 10.7- 113.6 µmol × 10-2/mL) and MBC at 42.7-358.6 µmol × 10-2/mL and 21.4-247.2 µmol × 10-2/mL, respectively. All the compounds exhibited antibacterial activity against the three resistant strains, MRSA, P. aeruginosa and E.coli. with MIC and MBC in the range of 0.65-11.00 µmol/mL × 10-2 and 1.30-16.50 µmol/mL × 10-2. Docking studies were performed.

Conclusion: Twenty-eight novel thiazole-based chalcones were designed, synthesized and evaluated for antimicrobial activity. The results showed that these derivatives could be lead compounds in search of new potent antimicrobial agents. Docking studies indicated that DNA gyrase, GyrB and MurA inhibition may explain the antibacterial activity.

Keywords: Thiazole, Chalcone, Antimicrobial, Antifungal, Microdilution, Docking, GyrB(1KZN), MurA, CYP51, Dihydrofolate reductase.

Tan, R.; Liu, J.; Li, M.; Huang, J.; Sun, J.; Qu, H. Epidemiology and antimicrobial resistance among commonly encountered bacteria associated with infections and colonization in intensive care units in a university-affiliated hospital in Shanghai. J. Microbiol. Immunol. Infect., 2014, 47(2), 87-94.
[] [PMID: 23357606]
Pfeltz, R.F. The Escalating Challenge of Vancomycin Resistance in Staphylococcus aureus. Curr. Drug Targets Infect. Disord., 2014, 4, 23-94.
Roberts, M.C. Distribution of macrolide, lincosamide, streptogramin, ketolide and oxazolidinone (MLSKO) resistance genes in Gram-negative bacteria. Curr. Drug Targets Infect. Disord., 2004, 4(3), 207-215.
[] [PMID: 15379732]
Dessen, A.; Di Guilmi, A.M.; Vernet, T.; Dideberg, O. Molecular mechanisms of antibiotic resistance in gram-positive pathogens. Curr. Drug Targets Infect. Disord., 2001, 1(1), 63-77.
[] [PMID: 12455234]
Johnson, A.P. Surveillance of antibiotic resistance. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2015, 370(1670), 20140080.
[] [PMID: 25918439]
Wahab Khan, M.; Jahangir Alam, M.; Rashid, M.A.; Chowdhury, R. A new structural alternative in benzo[b]furans for antimicrobial activity. Bioorg. Med. Chem., 2005, 13(16), 4796-4805.
[] [PMID: 15964760]
Ager, S.; Gould, K. Clinical update on linezolid in the treatment of Gram-positive bacterial infections. Infect. Drug Resist., 2012, 5, 87-102.
[PMID: 22787406]
Livermore, D.M. Linezolid in vitro: mechanism and antibacterial spectrum. J. Antimicrob. Chemother., 2003, 51(Suppl. 2), ii9-ii16.
[] [PMID: 12730138]
Anstead, G.M.; Owens, A.D. Recent advances in the treatment of infections due to resistant Staphylococcus aureus. Curr. Opin. Infect. Dis., 2004, 17(6), 549-555.
[] [PMID: 15640709]
Turan-Zitouni, G.; Altıntop, M.D.; Özdemir, A.; Kaplancıklı, Z.A.; Çiftçi, G.A.; Temel, H.E. Synthesis and evaluation of bis-thiazole derivatives as new anticancer agents. Eur. J. Med. Chem., 2016, 107, 288-294.
[] [PMID: 26599534]
Dhumal, S.T.; Deshmukh, A.R.; Bhosle, M.R.; Khedkar, V.M.; Nawale, L.U.; Sarkar, D.; Mane, R.A. Synthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds. Bioorg. Med. Chem. Lett., 2016, 26(15), 3646-3651.
[] [PMID: 27301367]
Duan, L.M.; Yu, H.Y.; Li, Y.L.; Jia, C.J. Design and discovery of 2-(4-(1H-tetrazol-5-yl)-1H-pyrazol-1-yl)-4-(4-phenyl)thiazole derivatives as cardiotonic agents via inhibition of PDE3. Bioorg. Med. Chem., 2015, 23(18), 6111-6117.
[ 10.1016/j.bmc.2015.08.002] [PMID: 26319621]
Argyropoulou, I.; Geronikaki, A.; Vicini, P. Zani, F. Synthesis and Biological Evaluation of Sulfonamide Thiazole and Benzothiazolyl Derivatives as Potent Antimicrobial Agents. ARKIVOC, 2009, 6, 89-102.
Camoutsis, C.; Geronikaki, A.; Ciric, A.; Soković, M.; Zoumpoulakis, P.; Zervou, M. Sulfonamide-1,2,4-thiadiazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies. Chem. Pharm. Bull. (Tokyo), 2010, 58(2), 160-167.
[] [PMID: 20118573]
Pawar, C.D.; Sarkate, A.P.; Karnik, K.S.; Bahekar, S.S.; Pansare, D.N.; Shelke, R.N.; Jawale, C.S.; Shinde, D.B. Synthesis and antimicrobial evaluation of novel ethyl 2-(2-(4-substituted)-acetamido)-4-subtituted-thiazole-5-carboxylate derivatives. Bioorg. Med. Chem. Lett., 2016, 26(15), 3525-3528.
[ 10.1016/j.bmcl.2016.06.030] [PMID: 27324976]
Mohammad, H.; Reddy, P.V.; Monteleone, D.; Mayhoub, A.S.; Cushman, M.; Seleem, M.N. Synthesis and antibacterial evaluation of a novel series of synthetic phenylthiazole compounds against methicillin-resistant Staphylococcus aureus (MRSA). Eur. J. Med. Chem., 2015, 94, 306-316.
[ 2015.03.015] [PMID: 25771109]
Liaras, K.; Geronikaki, A.; Glamočlija, J.; Cirić, A.; Soković, M. Thiazole-based chalcones as potent antimicrobial agents. Synthesis and biological evaluation. Bioorg. Med. Chem., 2011, 19(10), 3135-3140.
[] [PMID: 21524583]
Desai, N.C.; Atul, M. 2 Rajpara, K.Synthesis and study of 1,3,5-triazine based thiazole derivatives as antimicrobial agents. J. Saudi Chem. Soc., 2016, 20, S334-S41.
Omar, K.; Geronikaki, A.; Zoumpoulakis, P.; Camoutsis, C.; Soković, M.; Cirić, A.; Glamoclija, J. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorg. Med. Chem., 2010, 18(1), 426-432.
[] [PMID: 19914077]
Liaras, K.; Geronikaki, A.; Glamočlija, J.; Cirić, A.; Soković, M. Novel (E)-1-(4-methyl-2-(alkylamino)thiazol-5-yl)-3-arylprop-2-en-1-ones as potent antimicrobial agents. Bioorg. Med. Chem., 2011, 19(24), 7349-7356.
[] [PMID: 22079864]
Hänel, H.; Raether, W. A more sophisticated method of determining the fungicidal effect of water-insoluble preparations with a cell harvester, using miconazole as an example. Mycoses, 1988, 31(3), 148-154.
[] [PMID: 3292912]
Espinel-Ingroff, A. Comparison of the E-test with the NCCLS M38-P method for antifungal susceptibility testing of common and emerging pathogenic filamentous fungi. J. Clin. Microbiol., 2001, 39(4), 1360-1367.
[] [PMID: 11283057]
Ganou, C.A.; Eleftheriou, P.T.; Theodosis-Nobelos, P.; Fesatidou, M.; Geronikaki, A.A.; Lialiaris, T.; Rekka, E.A. Docking analysis targeted to the whole enzyme: an application to the prediction of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives. SAR QSAR Environ. Res., 2018, 29(2), 133-149.
[ 10.1080/1062936X.2017.1414874] [PMID: 29347844]
Tzeli, D.; Kozielewicz, P.; Zervou, M.; Potamitis, C.; Kokkotou, K.; Rak, B.; Petrou, A.; Tsolaki, E.; Gavalas, A.; Geronikaki, A.; Petsalakis, I.D.; Tsoungas, P. ChemistrySelect, 2016, 1, 2426-2438.
Kartsev, V.; Geronikaki, A.; Petrou, A.; Lichitsky, B.; Smiljkovic, M.; Kostic, M.; Radanovic, O.; Soković, M. MedChemCom., in press
Abdullah, M.I.; Mahmood, A.; Madni, M.; Masood, S.; Kashif, M. Synthesis, characterization, theoretical, anti-bacterial and molecular docking studies of quinoline based chalcones as a DNA gyrase inhibitor. Bioorg. Chem., 2014, 54, 31-37.
[] [PMID: 24747187]
Manivannan, C.; Santhi, N. Synthesis, Characterization, Molecular Docking Studies and Antibacterial Evaluation of Chalcone Based Pyrazolines as DNA Gyrase Inhibitors. Int. J. Modn. Res. Revs., 2015, 3(5), 679-687.
Stana, A.; Vodnar, D.C.; Tamaian, R.; Pîrnău, A.; Vlase, L.; Ionuț, I.; Oniga, O.; Tiperciuc, B. Design, Synthesis and Antifungal Activity Evaluation of New Thiazolin-4-ones as Potential Lanosterol 14α-Demethylase Inhibitors. Int. J. Mol. Sci., 2017, 18(1), 177-202.
[] [PMID: 28106743]
Kaplancıklı, Z.A.; Levent, S.; Osmaniye, D.; Sağlık, B.N.; Çevik, U.A.; Çavuşoğlu, B.K.; Özkay, Y.; Ilgın, S. Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives. Molecules, 2017, 22(12), 2051-2065.
[ 10.3390/molecules22122051] [PMID: 29168743]
Osmaniye, D.; Kaya Çavuşoğlu, B.; Sağlık, B.N.; Levent, S.; Acar Çevik, U.; Atlı, Ö.; Özkay, Y.; Kaplancıklı, Z.A. Synthesis and Anticandidal Activity of New Imidazole-Chalcones. Molecules, 2018, 23(4), 831-844.
[] [PMID: 29617329]

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Year: 2019
Page: [356 - 375]
Pages: 20
DOI: 10.2174/1568026619666190129121933
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