Приказ основних података о дисертацији
Istraživanje antimikrobne aktivnosti i hromatografskog ponašanja sastojaka endofitnih gljiva primenom hemometrijskih metoda
Investigation of antimicrobial activity and chromatographic behavior of endophytic fungi constituents using chemometric methods
dc.contributor.advisor | Otašević, Biljana | |
dc.contributor.other | Štrukelj, Borut | |
dc.contributor.other | Zečević, Mira | |
dc.contributor.other | Protić, Ana | |
dc.contributor.other | Filipić, Brankica | |
dc.creator | Ignjatović, Janko | |
dc.date.accessioned | 2023-05-18T12:56:12Z | |
dc.date.available | 2023-05-18T12:56:12Z | |
dc.date.issued | 2022-09-29 | |
dc.identifier.uri | https://eteze.bg.ac.rs/application/showtheses?thesesId=9083 | |
dc.identifier.uri | https://fedorabg.bg.ac.rs/fedora/get/o:29313/bdef:Content/download | |
dc.identifier.uri | https://plus.cobiss.net/cobiss/sr/sr/bib/77500937 | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/21428 | |
dc.description.abstract | Rezistencija bakterija na delovanje antibiotika predstavlja globalni problem. Na polju razvoja novih lekova iz prirodnih izvora, nedavno je prepoznat potencijal endofitnih gljiva zahvaljujući sposobnosti da proizvedu sekundarne metabolite različitih bioloških aktivnosti. Biosinteza ovih jedinjenja je pod velikim uticajem brojnih faktora koji se vezuju za izbor biljke domaćina, klimatske uslove, ishranu i prisustvo drugih mikroorganizama u okruženju. Velika baza podataka vezanih za aktivnost endofitnih gljiva prema patogenim bakterijama pretaživana je primenom metode analize glavnih komponenti sa ciljem pronalaženja obrazaca u podacima koji bi ukazali na manji broj pravih kandidata za novih razvoj lekova. Na ovaj način, osvetljen je antimikrobni karakter gljive Phomopsis species. In vitro testovima je potvrđeno da dihlormetanski ekstrakt gljive izolovane iz četina bora inhibira rast bakterija Escherichia coli i Staphylococcus aureus. Hromatografsko razdvajanje pojedinačnih jedinjenja ekstrakta optimizovano je primenom dizajna eksperimenata, a zatim je izvršeno izolovanje i karakterizacija njihove hemijske strukture korišćenjem masene spektrometrije i NMR spektroskopije. In silico metodama su definisani prediktori bioraspoloživosti i toksikološke aktivnosti jedinjenja (Z)-(Z)-2-acetoksiprop-1-en-1-il-3-(3-((E)-3,4-dihidroksipent-1-en-1- il)oksiran-2-il)akrilat i (Z)-(Z)-2-acetoksiprop-1-en-1-il-(3-((E)-4-hidroksi-3-oksopent-1-en-1- il)oksiran-2-il)akrilat. Za razliku od dosadašnih istraživanja koja su se ograničavala in vitro testovima antimikrobne aktivnosti endofitnih gljiva i razrešavanjem hemijske strukture izolovanih biomolekula, ova disertacija predstavlja proširenje prethodnih istraživanja primenom in silico metoda. Studija molekulskog dokinga omogućila je razumevanje mehanizama interakcije biomolekula sa receptorima koji pripadaju patogenim bakterijama uobičajeno multirezistentnim na antibiotike. Primenom veštačkih neuronskih mreža nagrađeni su pouzdani modeli koji ukazuju na vezu između hemijske strukture, parametara interakcije i afiniteta vezivanja za receptore na osnovu kojih je moguć razvoj novih hemijski srodnih antibiotika. | sr |
dc.description.abstract | Bacterial resistance towards antibiotics represents a global phenomenon. Potential of endophytic fungi as producers of secondary metabolites with wide spectra of different bioactivities in the field of drug discovery from natural resources has recently been introduced. The production of these compounds is under great impact of variety of factors related to the choice of plant host, climate conditions, nutrition and presence of other microorganisms in the same surrounding. Big data set comprising of indices of endophytic fungi antibacterial activity towards patogen bacteria was evaluated using principal component analysis with the aim to find patterns in data and to point out to a limited number of proper candidates for future pharmaceutical research. This resulted in highlightening of the antimicrobial character of Phomopsis species. In vitro tests proved that dichloromethane extract of endophytic fungi isolated from conifer needles inhibits the growth of Escherichia coli and Staphylococcus aureus. Chromatographic separation of individual components of extract was optimized using design of experiments followed by the isolation and chemical structure characterization using mass spectrometry and NMR spectroscopy. In silico methods were used to define the predictors of bioavaliability and toxicological activity of compounds (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3- (3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate and (Z)-(Z)-2-acetoxyprop-1-en-1- yl-3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate. Unlike up to date research outcomes limited to in vitro evaluation of antimicrobial activity of endophytic fungi and chemical structure elucidation of isolated biomolecules, this disertation represents an extension to previous investigations using in silico methods. The molecular docking study enabled the comprehensive understanding of the mechanisms underlying the interaction of biomolecules with receptors belonging to usually multidrug resistant bacterial pathogens. The artificial neural networks were used to build reliable models relating chemical structure, parameters of interaction and the binding affinity to receptors, thus providing the essence for future development of new chemically related antibiotics. | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Београду, Фармацеутски факултет | sr |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Универзитет у Београду | sr |
dc.subject | Antibakterijska aktivnost | sr |
dc.subject | Antibacterial activity | en |
dc.subject | Endophytic fungi | en |
dc.subject | Chemometric methods in pharmaceutical research | en |
dc.subject | in silico drug discovery | en |
dc.subject | Endofitne gljive | sr |
dc.subject | Hemometrijske metode u farmaceutskom istraživanju | sr |
dc.subject | in silico razvoj lekova | sr |
dc.title | Istraživanje antimikrobne aktivnosti i hromatografskog ponašanja sastojaka endofitnih gljiva primenom hemometrijskih metoda | sr |
dc.title.alternative | Investigation of antimicrobial activity and chromatographic behavior of endophytic fungi constituents using chemometric methods | en |
dc.type | doctoralThesis | |
dc.rights.license | BY-NC-ND | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/150925/Disertacija_13523.pdf | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/152751/Referat.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_21428 |