Računalniško modeliranje antikarcinogenih učinkov naringenina

diplomsko delo univerzitetnega študijskega programa I. stopnje

Lamija Ahmetović (Author), Urban Bren (Mentor), Veronika Furlan (Co-mentor)

Abstract

Naringenin je biološko aktiven polifenol iz citrusov z različnimi koristnimi učinki za človeško zdravje. Nedavna znanstvena literatura poroča, da naringenin lahko zavira razvoj in napredovanje tumorjev, kar kaže na njegov potencial za zdravljenje različnih vrst raka. To diplomsko delo je osredotočeno na naringenin v vlogi polifenolnega lovilca devetih končnih kemijskih karcinogenov, in sicer aflatoksin B1 ekso-8,9-epoksida, 2-cianoetilen oksida, etilen oksida, glicidamida, kloroetilen oksida, vinilkarbamat epoksida, stiren oksida, propilen oksida in β-propiolaktona. Cilj je izračunati aktivacijske proste energije in razjasniti molekularne mehanizme reakcij alkilacije naringenina z obravnavanimi genotoksičnimi kemijskimi karcinogeni z uporabo kvantno-mehanske metode Hartree-Fock v kombinaciji z dvema fleksibilnima baznima setoma 6-31G(d) in 6-311++G(d,p). Izračune aktivacijskih prostih energij smo izvedli na superračunalniški gruči VRANA s programom Gaussian 09 v vakuumu in z uporabo dveh implicitnih modelov topil: modela polarizabilnega kontinuuma in Langevinovih dipolov. Za oceno učinkovitosti naringenina kot polifenolnega lovilca smo izračunane aktivacijske proste energije v kombinaciji z modeli topil primerjali z eksperimentalnimi vrednostmi aktivacijskih prostih energij med istimi končnimi kemijskimi karcinogeni in najbolj reaktivno DNK bazo gvaninom. Rezultati kažejo na učinkovitost naringenina kot polifenolnega lovilca šestih končnih kemijskih karcinogenov, pri čemer najbolj izstopajo β-propiolakton, vinilkarbamat epoksid in propilen oksid. Znaten antikarcinogeni potencial je naringenin izkazal tudi kot lovilec kloroetilen oksida, aflatoksin B1-ekso-8,9-epoksida in etilen oksida, v primeru katerih so bile izračunane aktivacijske proste energije podobne z eksperimentalno določenimi vrednostmi. V primeru 2-cianoetilen oksida, glicidamida in stiren oksida zaščitne lastnosti naringenina niso tako izrazite, saj so bile izračunane aktivacijske proste energije višje v primerjavi z eksperimentalno določenimi vrednostmi za gvanin. Trdno verjamemo, da je diplomsko delo razjasnilo zapletene molekularne mehanizme naringenina in bo imelo velik vpliv na nadaljnje računalniške in eksperimentalne študije njegovih antikarcinogenih učinkov.

Keywords

naringenin;flavanoni;končni kemijski karcinogeni;aktivacijske proste energije;kvantno-mehanski izračuni;metoda Hartree-Fock;implicitni solvatacijski modeli;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2024
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[L. Ahmetović]
UDC:	604.4:615.277.3(043.2)
COBISS:	204922371
Views:	119
Downloads:	30
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Computational modeling of anticarcinogenic effects of naringenin
Secondary abstract:	Naringenin represents a bioactive polyphenol from citrus fruits with various beneficial effects on human health. Recent scientific literature reports that naringenin can suppress tumor development and progression, indicating its potential for the treatment of different types of cancer. This bachelor thesis is focused on naringenin as a polyphenolic scavenger of nine ultimate chemical carcinogens, namely aflatoxin B1 exo-8,9-epoxide, 2-cyano ethylene oxide, ethylene oxide, glycidamide, chloroethylene oxide, vinyl carbamate epoxide, styrene oxide, propylene oxide, and β-propiolactone. The aim is to calculate the activation free energies and elucidate molecular mechanisms of alkylation reactions of naringenin with the studied genotoxic chemical carcinogens using the quantum-mechanical method Hartree-Fock in combination with two flexible basis sets 6-31G(d) and 6-311++G(d,p). Activation free energy calculations were performed on Slovenian supercomputer cluster VRANA with the program Gaussian 09 in vacuum as well as using two implicit solvation models: Polarizable Continuum Model and Langevin Dipoles. To evaluate the scavenging efficacy of naringenin, the activation-free energies calculated in combination with solvation models were compared with the experimental values of the activation free energies between the same ultimate chemical carcinogens and the most reactive DNA base guanine. The findings indicate naringenin's efficacy as a polyphenolic scavenger of six ultimate chemical carcinogens, especially: β-propiolactone, vinylcarbamate epoxide, and propylene oxide. For chloroethylene oxide, aflatoxin B1-exo-8,9-epoxide, and ethylene oxide, naringenin's anti-carcinogenic potential is also significantly pronounced as the calculated activation free energies were similar to experimentally determined values for guanine. However, naringenin's protective activity is not as potent against 2-cyanoethylene oxide, glycidamide, and styrene oxide, as the activation free energies were considerably higher compared to the experimentally determined ones for guanine. We firmly believe that this research work elucidated intricate molecular mechanisms of naringenin and is expected to have a vast impact on further computational as well as experimental studies of its anti-carcinogenic effects.
Secondary keywords:	naringenin;flavanones;ultimate chemical carcinogens;activation free energies;quantum-mechanical calculations;Hartree-Fock method;implicit solvation models;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	1 spletni vir (1 datoteka PDF (X, 38 f.))
ID:	24281042