[6]-gingerol kot naravni lovilec kemijskih karcinogenov - računalniški pristop

Furlan, Veronika

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Title:	[6]-gingerol kot naravni lovilec kemijskih karcinogenov - računalniški pristop
Authors:	ID Furlan, Veronika (Author) ID Bren, Urban (Mentor) More about this mentor... ID Španinger, Eva (Comentor)
Files:	MAG_Furlan_Veronika_2017.pdf (2,30 MB) MD5: 3515C4056630927091A371E6D26B3703 PID: 20.500.12556/dkum/b1a82ba9-9a79-449d-b87f-02c7630fdb62
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:	V magistrski nalogi smo se posvetili preučevanju [6]-gingerola iz ingverja kot polifenolnega lovilca devetih končnih kemijskih karcinogenov aflatoksin B1 ekso-8,9-epoksida, β-propiolaktona, 2-cianoetilen oksida, etilen oksida, kloroetilen oksida, glicidamida, propilen oksida, stiren oksida in vinil karbamat epoksida. Za oceno učinkovitosti [6]-gingerola smo raziskavo razširili še z obravnavo najmočnejšega lovilca kemijskih karcinogenov v našem telesu - glutationa. V magistrskem delu smo s pomočjo računalniških simulacij preučili mehanizme reakcij med kemijskimi karcinogeni in [6]-gingerolom oz. glutationom, pri čemer smo izračune aktivacijskih prostih energij izvedli z uporabo kvantnomehanske metode Hartree-Fock pri treh različnih baznih setih. Naša študija nakazuje, da [6]-gingerol predstavlja univerzalen in izredno učinkovit naravni lovilec kemijskih karcinogenov epoksidnega tipa. Aktivacijske proste energije, dobljene po solvatacijskih metodah Samouglašenega reakcijskega polja in Langevinovih dipolov, ki so direktno primerljive z eksperimentalnimi podatki, so za reakcije vseh obravnavanih kemijskih karcinogenov s [6]-gingerolom nižje od eksperimentalno določenih aktivacijskih prostih energij za reakcije obravnavanih karcinogenov z najbolj reaktivno izmed organskih baz DNA- gvaninom. Izračuni aktivacijskih prostih energij ob upoštevanju solvatacijskih efektov nakazujejo, da nas glutation ne more učinkovito zaščititi pred vsemi obravnavanimi kemijskimi karcinogeni. Dobljene aktivacijske proste energije so bile namreč večinoma višje od eksperimentalno določenih aktivacijskih prostih energij za reakcije obravnavanih karcinogenov z gvaninom. V primerjavi z glutationom se je [6]-gingerol izkazal kot učinkovitejši lovilec osmih obravnavanih kemijskih karcinogenov, le pri reakciji alkilacije z aflatoksin B1 ekso-8,9-epoksidom [6]-gingerol in glutation predstavljata enakovredno učinkovita lovilca. Dobljeni rezultati potrjujejo tudi hipotezo, da reakcije alkilacije med obravnavanimi kemijskimi karcinogeni in [6]-gingerolom oz. glutationom potekajo po mehanizmu nukleofilne substitucije SN2. Dobljene aktivacijske proste energije ob upoštevanju solvatacijskih efektov potrjujejo, da za preprečitev iniciacije karcinogeneze, ki jo povzročajo obravnavane rakotvorne spojine iz vsakdanjega življenja, potrebujemo dodatno zaščito, ki jo lahko zagotovi [6]-gingerol. Verjamemo, da naša raziskava predstavlja izhodišče za nadaljnje računalniške, eksperimentalne in klinične študije antikarcinogenih učinkov [6]-gingerola ter za razvoj novih selektivnih prehranskih dopolnil.
Keywords:	[6]-gingerol, glutation, kemijski karcinogeni, karcinogeneza, aktivacijska prosta energija, kvantnomehanske simulacije
Place of publishing:	Maribor
Publisher:	[V. Furlan]
Year of publishing:	2017
PID:	20.500.12556/DKUM-67691
UDC:	615.227:004.414.23(043.2)
COBISS.SI-ID:	20858646
NUK URN:	URN:SI:UM:DK:VBJRO4CU
Publication date in DKUM:	18.09.2017
Views:	2140
Downloads:	645
Metadata:
Categories:	KTFMB - FKKT
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	28.08.2017

Secondary language

Language:	English
Title:	[6]-gingerol as a natural scavenger of chemical carcinogens - a computational approach
Abstract:	In the master thesis, we examined [6]-gingerol from ginger as a polyphenolic scavenger of nine ultimate chemical carcinogens aflatoxin B1 ekso-8,9-epoxide, β-propiolactone, 2-cyanoethylene oxide, ethylene oxide, chloroethylene oxide, glycidamide, propylene oxide, styrene oxide and vinyl carbamate epoxide. To evaluate [6]-gingerol efficiency, we expanded our research with examination of glutathione - the strongest scavenger of chemical carcinogens in human bodies. Furthermore, we examined mechanisms of chemical reactions of [6]-gingerol and glutathione with chemical carcinogens. The ab initio calculations of activation free energies were performed at the Hartree-Fock level of theory in conjunction with three different basis sets. According to our research, [6]-gingerol proves to be a universal and extremely efficient natural scavenger of chemical carcinogens of the epoxy type. Activation free energies, obtained with solvation methods Self-consistent reaction field and Langevin dipoles, are comparable with the experimental results. Moreover, experimentally obtained activation free energies for reactions of chemical carcinogens with the most reactive DNA base guanine were higher than the obtained activation free energies for the reactions of chemical carcinogens with [6]-gingerol. Activation free energies obtained by quantum-chemical simulations with included solvation effects, suggest that glutathione cannot efficiently protect us from all chemical carcinogens. Namely, most of the obtained activation free energies for the reactions with glutathione were higher than the experimentally obtained activation free energies for reactions of chemical carcinogens with guanine. In comparison with glutathione, [6]-gingerol proved to be a more efficient natural scavenger of eight chemical carcinogens. The only exception was the alkylation reaction with aflatoxin B1 ekso-8,9-epoxide, where [6]-gingerol and glutathione performed equally well. Obtained results present strong evidence in favor of the validity of the proposed SN2 reaction mechanism for the alkylation reactions of [6]-gingerol and glutathione with chemical carcinogens. Furthermore, our results obtained with solvation methods imply, that additional protection is required for prevention of carcinogenesis triggered by chemical carcinogens. Based on our results, additional protection can be assured by ingestion of [6]-gingerol. We strongly believe that our research represents the basis for further computational, experimental and clinical studies of anti-carcinogenic properties of [6]-gingerol and for development of novel selective dietary supplements.
Keywords:	[6]-gingerol, glutathione, chemical carcinogens, carcinogenesis, activation free energy, quantum-chemical simulations

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