- citati u SCIndeksu: 0
- citati u CrossRef-u:0
- citati u Google Scholaru:[
 ]
- posete u poslednjih 30 dana:7
- preuzimanja u poslednjih 30 dana:6
|
|
|
2021, vol. 10, br. 2, str. 14-23
|
|
Sinteza, karakterizacija i procena antioksidativne i antimikrobne aktivnosti tri nova n-heteroaromatična hidrazonil-tiazola
Synthesis, characterization, and evaluation of antioxidant and antimicrobial activity of three novel n-heteroaromatic hydrazonyl-thiazoles
aUniverzitet u Beogradu, Hemijski fakultet, Srbija bUniverzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM, Srbija cUniverzitet u Beogradu, Poljoprivredni fakultet, Srbija
e-adresa: nenadf@agrif.bg.ac.rs
Projekat: Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije (institucija: Inovacioni centar Hemijskog fakulteta u Beogradu doo) (MPNTR - 451-03-68/2020-14/200288)
Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije (institucija: Univerzitet u Beogradu, Hemijski fakultet) (MPNTR - 451-03-68/2020-14/200168)
Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije (institucija: Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (MPNTR - 451-03-68/2020-14/200026)
Sažetak
(Tiazolil-2-il)-hidrazoni (TH) su grupa organskih jedinjenja koja sadrže i hidrazon i 1,3-tiazol farmakofore koje su prisutne u mnogim odobrenim lekovima. Poslednjih godina se u velikoj meri istražuju zbog jakih antikancerogenih, antibakterijskih, antifungalnih, antituberkuloznih, antiinflamatornih i antiparazitskih aktivnosti. U ovoj studiji, sintetisan je jedan novi TH na bazi piridina i dva na bazi hinolina, koji su okarakterisani elementalnom analizom, infracrvenom spektroskopijom sa Furijeovom transformacijom (FTIR) i spektroskopijom nuklearne magnetne rezonancije (NMR). Antimikrobna aktivnost jedinjenja je testirana na pet Gram-pozitivnih i pet Gram-negativnih bakterijskih sojeva, kao i na tri soja gljivica. Šest antioksidativnih testova je korišćeno za određivanje antioksidativnog kapaciteta sintetisanih jedinjenja. Rezultati su pokazali da su TH na bazi hinolina aktivniji prema testiranim Gram-negativnim sojevima bakterija i prema gljivicama, nego jedinjenja na bazi piridina. Sva jedinjenja su pokazala odlično antioksidativno dejstvo, uporedivo ili veće od korišćenih standarda (vitamin C i troloks). Parametri apsorpcije, distribucije, metabolizma, izlučivanja i toksičnosti (ADME) izračunati su in-silico. Rezultati ukazuju na dobre farmakokinetičke profile ispitivanih jedinjenja, posebno jedinjenja na bazi 2-hinolinkarboksaldehida koje ima potencijal da bude kandidat za osnovno jedinjenje (engl. lead compound).
Abstract
(Thiazolyl-2-yl)hydrazones (THs) are a group of organic compounds containing both hydrazone and 1,3-thiazole pharmacophores present in many approved drugs. They have been investigated greatly in recent years due to potent anticancer, antibacterial, antifungal, antituberculosis, anti-inflammatory, and antiparasitic activities. In this study, one pyridine-based and two quinoline-based, novel THs were synthesized and characterized by elemental analysis, Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR). The antimicrobial activity of the compounds was tested against five Gram-positive and five Gram-negative bacteria, as well as against three fungi. The antioxidant capacity of the compounds was tested in six antioxidative assays. The results showed that quinoline-based THs were more active against tested Gram-negative bacteria and fungi strains than pyridine-based compounds. All the compounds showed excellent antioxidative activity comparable to or greater than the used standards (vitamin C and Trolox). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were calculated in-silico. Results pointed to promising good pharmacokinetics profiles of investigated compounds, especially 2-quinoline carboxaldehyde-based compound, which can be a lead drug candidate.
|
|
|
|
Reference
|
|
  
|
Aldrich, C., Bertozzi, C., Georg, G.I., Kiessling, L., Lindsley, C., Liotta, D., Merz, K.M., Schepartz, A., Wang, S. (2017) The Ecstasy and Agony of Assay Interference Compounds. Journal of Medicinal Chemistry, 60(6): 2165-2168
|
|
|
Anthony, K.P., Saleh, M.A. (2013) Free Radical Scavenging and Antioxidant Activities of Silymarin Components. Antioxidants, 2(4): 398-407
|
|
|
Araškov, J.B., Nikolić, M., Armaković, S., Armaković, S., Rodić, M., Višnjevac, A., Padrón, J.M., Todorović, T.R., Filipović, N.R. (2021) Structural, antioxidant, antiproliferative and in-silico study of pyridine-based hydrazonyl-selenazoles and their sulphur isosteres. Journal of Molecular Structure, 1240: 130512-130512
|
|
|
Bisceglie, F., Musiari, A., Pinelli, S., Alinovi, R., Menozzi, I., Polverini, E., Tarasconi, P., Tavone, M., Pelosi, G. (2015) Quinoline-2-carboxaldehyde thiosemicarbazones and their Cu(II) and Ni(II) complexes as topoisomerase IIa inhibitors. Journal of Inorganic Biochemistry, 152: 10-19
|
|
|
Bollgon, A.A., Machado, M.M., Athayde, M.L. (2014) Technical Evaluation of Antioxidant Activity. Medicinal Chemistry, 4(7): 517-522
|
|
|
Chandra, S., Raizada, S., Tyagi, M., Sharma, P.K. (2008) Spectroscopic and biological approach of Ni(II) and Cu(II) complexes of 2-pyridinecarboxaldehyde thiosemicarbazone. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 69(3): 816-821
|
|
4
|
Daina, A., Michielin, O., Zoete, V. (2017) SwissADME: A free Web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1): 42717-42717
|
|
|
Elshaflu, H., Bjelogrlić, S., Muller, C.D., Todorović, T.R., Rodić, M., Marinković, A., Filipović, N.R. (2016) Co(III) complex with (E)-2-(2-(pyridine-2-ylmethylene)hydrazinyl)-4-(4-tolyl)-1,3-thiazole: structure and activity against 2-D and 3-D cancer cell models. Journal of Coordination Chemistry, 69(22): 3354-3366
|
|
|
European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectio (2003) Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution. Clinical Microbiology and Infection, 9 (8) IX-XV
|
|
|
Filipović, N., Todorović, T., Marković, R., Marinković, A., Tufegdžić, S., Gođevac, D., Anđelković, K. (2010) Synthesis, characterization and biological activities of N-heteroaromatic hydrazones and their complexes with Pd(II), Pt(II) and Cd(II). Transition Metal Chemistry, 35(6): 765-772
|
|
|
Filipović, N.R., Elshaflu, H., Grubišić, S., Jovanović, L.S., Rodić, M., Novaković, I., Malešević, A.S., Đorđević, I.S., Li, H., Šojić, N., Marinković, A.R., Todorović, T.R. (2017) Co(III) complexes of (1,3-selenazol-2-yl)hydrazones and their sulphur analogues. Dalton Transactions, 46(9): 2910-2924
|
|
|
Forli, S. (2014) Epothilones: From Discovery to Clinical Trials. Current Topics in Medicinal Chemistry, 14(20): 2312-2321
|
|
|
Gulcin, I. (2020) Antioxidants and antioxidant methods: An updated overview. Archives of Toxicology, 94(3): 651-715
|
|
|
Habu, J.B., Ibeh, B.O. (2015) In vitro antioxidant capacity and free radical scavenging evaluation of active metabolite constituents of Newbouldia laevis ethanolic leaf extract. Biological Research, 48(1): 16-16
|
|
|
Hastings, W. (1996) Chemistries and colors of bioluminescent reactions: A review. Gene, 173(1): 5-11
|
|
|
Kalam, S., Gul, M.Z., Singh, R., Ankati, S. (2015) Free Radicals: Implications in Etiology of Chronic Diseases and Their Amelioration through Nutraceuticals. Pharmacologia, 6, 11-20
|
|
|
Kowol, C.R., Miklos, W., Pfaff, S., Hager, S., Kallus, S., Pelivan, K., Kubanik, M., Enyedy, É.A., Berger, W., Heffeter, P., Keppler, B.K. (2016) Impact of Stepwise NH2-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention. Journal of Medicinal Chemistry, 59(14): 6739-6752
|
|
4 
|
Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, P.J. (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced drug delivery reviews, 46(1-3): 3-26
|
|
|
Mak, J.Y.W., Xu, W., Fairlie, D.P. (2015) Peptidomimetics. u: Topics in Heterocyclic Chemistry, Berlin-Heidelberg: Springer, I, p. 235-266
|
|
|
Müller, J., Martins, A., Csábi, J., Fenyvesi, F., Könczöl, Á., Hunyadi, A., Balogh, G.T. (2017) BBB penetration-targeting physicochemical lead selection: Ecdysteroids as chemo-sensitizers against CNS tumors. European Journal of Pharmaceutical Sciences, 96: 571-577
|
|
|
Ou, B., Hampsch-Woodill, M., Prior, R.L. (2001) Development and Validation of an Improved Oxygen Radical Absorbance Capacity Assay Using Fluorescein as the Fluorescent Probe. Journal of Agricultural and Food Chemistry, 49(10): 4619-4626
|
|
|
Ou, B., Hampsch-Woodill, M., Flanagan, J., Deemer, E.K., Prior, R.L., Huang, D. (2002) Novel Fluorometric Assay for Hydroxyl Radical Prevention Capacity Using Fluorescein as the Probe. Journal of Agricultural and Food Chemistry, 50(10): 2772-2777
|
|
|
Petrou, A., Fesatidou, M., Geronikaki, A. (2021) Thiazole Ring: A Biologically Active Scaffold. Molecules, 26(11): 3166-3166
|
|
8
|
Prieto, P., Pineda, M., Aguilar, M. (1999) Spectrophotometric Quantitation of Antioxidant Capacity through the Formation of a Phosphomolybdenum Complex: Specific Application to the Determination of Vitamin E. Analytical Biochemistry, 269(2): 337-341
|
|
6
|
Prior, R.L., Wu, X., Schaich, K. (2005) Standardized Methods for the Determination of Antioxidant Capacity and Phenolics in Foods and Dietary Supplements. Journal of Agricultural and Food Chemistry, 53(10): 4290-4302
|
|
|
Rogolino, D., Cavazzoni, A., Gatti, A., Tegoni, M., Pelosi, G., Verdolino, V., Fumarola, C., Cretella, D., Petronini, P.G., Carcelli, M. (2017) Anti-proliferative effects of copper(II) complexes with hydroxyquinoline-thiosemicarbazone ligands. European Journal of Medicinal Chemistry, 128: 140-153
|
|
|
Sterling, T., Irwin, J.J. (2015) ZINC 15: Ligand Discovery for Everyone. Journal of Chemical Information and Modeling, 55(11): 2324-2337
|
|
|
|
|