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Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations

Aksić, Jelena; Genčić, Marija; Radulović, Niko; Dimitrijević, Marina; Stojanović-Radić, Zorica; Ilić Tomić, Tatjana; Rodić, Marko

(2023)

TY  - JOUR
AU  - Aksić, Jelena
AU  - Genčić, Marija
AU  - Radulović, Niko
AU  - Dimitrijević, Marina
AU  - Stojanović-Radić, Zorica
AU  - Ilić Tomić, Tatjana
AU  - Rodić, Marko
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0045206823003693
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2068
AB  - To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N-acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N-acylation step was highly diastereoselective toward the cis-diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn-orientation around the CN bond. A twisted 5T4 envelope conformation was adopted by the derivative containing the N-phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N-3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC50(MRC5) = 9.0 and 11.8 μM, respectively, and IC50(HepG2) = 10.6 and 18.4 μM, respectively) causing an effect similar to the lead compound (IC50(HepG2) = 10.0 μM) and cisplatin (IC50(MRC5) = 4.0 μM and IC50(HepG2) = 7.7 μM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 μmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N-acyl side-chain.
T2  - Bioorganic Chemistry
T1  - Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations
SP  - 106708
VL  - 139
DO  - 10.1016/j.bioorg.2023.106708
ER  - 
@article{
author = "Aksić, Jelena and Genčić, Marija and Radulović, Niko and Dimitrijević, Marina and Stojanović-Radić, Zorica and Ilić Tomić, Tatjana and Rodić, Marko",
year = "2023",
abstract = "To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N-acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N-acylation step was highly diastereoselective toward the cis-diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn-orientation around the CN bond. A twisted 5T4 envelope conformation was adopted by the derivative containing the N-phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N-3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC50(MRC5) = 9.0 and 11.8 μM, respectively, and IC50(HepG2) = 10.6 and 18.4 μM, respectively) causing an effect similar to the lead compound (IC50(HepG2) = 10.0 μM) and cisplatin (IC50(MRC5) = 4.0 μM and IC50(HepG2) = 7.7 μM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 μmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N-acyl side-chain.",
journal = "Bioorganic Chemistry",
title = "Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations",
pages = "106708",
volume = "139",
doi = "10.1016/j.bioorg.2023.106708"
}
Aksić, J., Genčić, M., Radulović, N., Dimitrijević, M., Stojanović-Radić, Z., Ilić Tomić, T.,& Rodić, M.. (2023). Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations. in Bioorganic Chemistry, 139, 106708.
https://doi.org/10.1016/j.bioorg.2023.106708
Aksić J, Genčić M, Radulović N, Dimitrijević M, Stojanović-Radić Z, Ilić Tomić T, Rodić M. Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations. in Bioorganic Chemistry. 2023;139:106708.
doi:10.1016/j.bioorg.2023.106708 .
Aksić, Jelena, Genčić, Marija, Radulović, Niko, Dimitrijević, Marina, Stojanović-Radić, Zorica, Ilić Tomić, Tatjana, Rodić, Marko, "Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations" in Bioorganic Chemistry, 139 (2023):106708,
https://doi.org/10.1016/j.bioorg.2023.106708 . .

A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas

Lazarević, Milica; Jovanović, Nikola; Cvetković, Vladimir J.; Tošić, Svetlana; Vitorović, Jelena; Stamenković, Slaviša; Nikolov, Vesna; Vidović, Nataša; Kostić Perić, Jelena; Jovanović, Marija; Mitrović, Tatjana

(2023)

TY  - JOUR
AU  - Lazarević, Milica
AU  - Jovanović, Nikola
AU  - Cvetković, Vladimir J.
AU  - Tošić, Svetlana
AU  - Vitorović, Jelena
AU  - Stamenković, Slaviša
AU  - Nikolov, Vesna
AU  - Vidović, Nataša
AU  - Kostić Perić, Jelena
AU  - Jovanović, Marija
AU  - Mitrović, Tatjana
PY  - 2023
UR  - https://www.mdpi.com/2075-4418/13/3/360
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1777
AB  - Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0—unmethylated and 1—weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss’ Kappa statistical analyses indicated moderate agreement (Fleiss’ Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss’ Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.
T2  - Diagnostics
T2  - Diagnostics
T1  - A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas
IS  - 3
SP  - 360
VL  - 13
DO  - 10.3390/diagnostics13030360
ER  - 
@article{
author = "Lazarević, Milica and Jovanović, Nikola and Cvetković, Vladimir J. and Tošić, Svetlana and Vitorović, Jelena and Stamenković, Slaviša and Nikolov, Vesna and Vidović, Nataša and Kostić Perić, Jelena and Jovanović, Marija and Mitrović, Tatjana",
year = "2023",
abstract = "Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0—unmethylated and 1—weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss’ Kappa statistical analyses indicated moderate agreement (Fleiss’ Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss’ Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.",
journal = "Diagnostics, Diagnostics",
title = "A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas",
number = "3",
pages = "360",
volume = "13",
doi = "10.3390/diagnostics13030360"
}
Lazarević, M., Jovanović, N., Cvetković, V. J., Tošić, S., Vitorović, J., Stamenković, S., Nikolov, V., Vidović, N., Kostić Perić, J., Jovanović, M.,& Mitrović, T.. (2023). A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas. in Diagnostics, 13(3), 360.
https://doi.org/10.3390/diagnostics13030360
Lazarević M, Jovanović N, Cvetković VJ, Tošić S, Vitorović J, Stamenković S, Nikolov V, Vidović N, Kostić Perić J, Jovanović M, Mitrović T. A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas. in Diagnostics. 2023;13(3):360.
doi:10.3390/diagnostics13030360 .
Lazarević, Milica, Jovanović, Nikola, Cvetković, Vladimir J., Tošić, Svetlana, Vitorović, Jelena, Stamenković, Slaviša, Nikolov, Vesna, Vidović, Nataša, Kostić Perić, Jelena, Jovanović, Marija, Mitrović, Tatjana, "A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas" in Diagnostics, 13, no. 3 (2023):360,
https://doi.org/10.3390/diagnostics13030360 . .

Molekularna dijagnostika glioblastoma –klinički uticaji IDH mutacija i epigenetičkog utišavanja aktivnosti MGMT gena

Jovanović, Nikola; Mitrović, Tatjana

(Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo, 2022)

TY  - CHAP
AU  - Jovanović, Nikola
AU  - Mitrović, Tatjana
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1817
AB  - Savremeni terapijski pristupi u lečenju pacijenata obolelih od glioblastoma (GBM) oslanjaju se
na primenu alkilirajućih agenasa poput Temozolomida (“Stupp”-ov protokol). Sveobuhvatnim studijama
izučavanja genomskih asocijacija (GWAS) i randomizovanim kliničkim ispitivanjima otkriven je
uticaj statusa nekoliko važnih molekularnih markera na terapijski odgovor i klinički ishod kod GBM
pacijenata. Najvažnijim takvim markerom smatra se status mutacije gena za izocitrat-dehidrogenazu
1 (IDH1-R132H), koji je uvršten u važeću Klasifikaciju tumora centralnog nervnog sistema Svetske
zdravstvene organizacije. Određivanjem njegovog statusa moguće je razlikovati primarne od sekundarnih
GBM koje odlikuju značajne razlike u toku i ishodu bolesti. Takođe, pokazano je da je IDH1-
R132H mutacija usko povezana sa mehanizmima epigenetičkog utišavanja aktivnosti gena za
reparacioni enzim O⁶-metilguanin-metiltransferazu (MGMT) putem metilacije njegovog promotornog
regiona. Zbog direktnog suprotstavljanja MGMT enzima dejstvu alkilirajućih agenasa, navedena inaktivacija
njegove aktivnosti predstavlja povoljan prognostički i predikcioni faktor GBM. Predmet
ovog revijskog rada biće pregled aktuelnih saznanja o ulozi navedenih markera u etiologiji GBM,
značaja njihove udružene evaluacije i problema šire implementacije njihovog određivanja u kliničkoj
praksi.
AB  - Current therapy protocols for the management of glioblastoma (GBM) patients mostly rely on the use
of alkylating agents, such as Temozolomide (Stupp protocol). During the past several decades, comprehensive
genome-wide association studies (GWAS) and randomized clinical trials have revealed and confirmed
the impact of numerous molecular markers on the therapy response in GBM patients. Among them,
the mutation status of the isocitrate dehydrogenase 1 gene (IDH1-R132H) was presented as the most important
molecular marker of GBM. Due to its importance, in 2016 it was introduced to the World Health Organisation
(WHO) Classification of Tumours of the Central Nervous System (CNS), which is still valid.
Through IDH1-R132H mutation evaluation, it is possible to distinguish the primary from the secondary
GBM which significantly differ in the clinical course and outcome. Moreover, it was shown that IDH1-R132H
mutation is closely related to the molecular mechanisms which drive epigenetic silencing of the O6-Methylguanine-
DNA Methyltransferase gene (MGMT) through methylation of its promoter region. Due to
the direct opposition of the MGMT enzyme to the alkylating agents‘ activity, its inactivation represents a
favorable prognostic and predictive factor in GBM. This review article discusses the current insights on the
role of IDH1 mutation and MGMT epigenetic silencing in GBM etiology, the importance of their mutual evaluation,
and the challenges of their evaluation in clinical practice.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Molekularna dijagnostika glioblastoma –klinički uticaji IDH mutacija i epigenetičkog utišavanja aktivnosti MGMT gena
T1  - Molecular diagnostics of glioblastoma – clinical impact of IDH mutations and epigenetic silencing of MGMT
EP  - 142
IS  - 2
SP  - 125
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1817
ER  - 
@inbook{
author = "Jovanović, Nikola and Mitrović, Tatjana",
year = "2022",
abstract = "Savremeni terapijski pristupi u lečenju pacijenata obolelih od glioblastoma (GBM) oslanjaju se
na primenu alkilirajućih agenasa poput Temozolomida (“Stupp”-ov protokol). Sveobuhvatnim studijama
izučavanja genomskih asocijacija (GWAS) i randomizovanim kliničkim ispitivanjima otkriven je
uticaj statusa nekoliko važnih molekularnih markera na terapijski odgovor i klinički ishod kod GBM
pacijenata. Najvažnijim takvim markerom smatra se status mutacije gena za izocitrat-dehidrogenazu
1 (IDH1-R132H), koji je uvršten u važeću Klasifikaciju tumora centralnog nervnog sistema Svetske
zdravstvene organizacije. Određivanjem njegovog statusa moguće je razlikovati primarne od sekundarnih
GBM koje odlikuju značajne razlike u toku i ishodu bolesti. Takođe, pokazano je da je IDH1-
R132H mutacija usko povezana sa mehanizmima epigenetičkog utišavanja aktivnosti gena za
reparacioni enzim O⁶-metilguanin-metiltransferazu (MGMT) putem metilacije njegovog promotornog
regiona. Zbog direktnog suprotstavljanja MGMT enzima dejstvu alkilirajućih agenasa, navedena inaktivacija
njegove aktivnosti predstavlja povoljan prognostički i predikcioni faktor GBM. Predmet
ovog revijskog rada biće pregled aktuelnih saznanja o ulozi navedenih markera u etiologiji GBM,
značaja njihove udružene evaluacije i problema šire implementacije njihovog određivanja u kliničkoj
praksi., Current therapy protocols for the management of glioblastoma (GBM) patients mostly rely on the use
of alkylating agents, such as Temozolomide (Stupp protocol). During the past several decades, comprehensive
genome-wide association studies (GWAS) and randomized clinical trials have revealed and confirmed
the impact of numerous molecular markers on the therapy response in GBM patients. Among them,
the mutation status of the isocitrate dehydrogenase 1 gene (IDH1-R132H) was presented as the most important
molecular marker of GBM. Due to its importance, in 2016 it was introduced to the World Health Organisation
(WHO) Classification of Tumours of the Central Nervous System (CNS), which is still valid.
Through IDH1-R132H mutation evaluation, it is possible to distinguish the primary from the secondary
GBM which significantly differ in the clinical course and outcome. Moreover, it was shown that IDH1-R132H
mutation is closely related to the molecular mechanisms which drive epigenetic silencing of the O6-Methylguanine-
DNA Methyltransferase gene (MGMT) through methylation of its promoter region. Due to
the direct opposition of the MGMT enzyme to the alkylating agents‘ activity, its inactivation represents a
favorable prognostic and predictive factor in GBM. This review article discusses the current insights on the
role of IDH1 mutation and MGMT epigenetic silencing in GBM etiology, the importance of their mutual evaluation,
and the challenges of their evaluation in clinical practice.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Molekularna dijagnostika glioblastoma –klinički uticaji IDH mutacija i epigenetičkog utišavanja aktivnosti MGMT gena, Molecular diagnostics of glioblastoma – clinical impact of IDH mutations and epigenetic silencing of MGMT",
pages = "142-125",
number = "2",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1817"
}
Jovanović, N.,& Mitrović, T.. (2022). Molekularna dijagnostika glioblastoma –klinički uticaji IDH mutacija i epigenetičkog utišavanja aktivnosti MGMT gena. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo.(2), 125-142.
https://hdl.handle.net/21.15107/rcub_imagine_1817
Jovanović N, Mitrović T. Molekularna dijagnostika glioblastoma –klinički uticaji IDH mutacija i epigenetičkog utišavanja aktivnosti MGMT gena. in Trendovi u molekularnoj Biologiji. 2022;(2):125-142.
https://hdl.handle.net/21.15107/rcub_imagine_1817 .
Jovanović, Nikola, Mitrović, Tatjana, "Molekularna dijagnostika glioblastoma –klinički uticaji IDH mutacija i epigenetičkog utišavanja aktivnosti MGMT gena" in Trendovi u molekularnoj Biologiji, no. 2 (2022):125-142,
https://hdl.handle.net/21.15107/rcub_imagine_1817 .

Citotoksični potencijal estara linoleinske kiseline detektovanih u odbrambenim sekretima stonoga Megaphyllum bosniense i M. unilineatum (Diplopoda: Julida)

Milovanović, Jelena; Ilić, Bojan; Radulović, Niko; Mladenović, Marko; Makarov, Slobodan; Divac Rankov, Aleksandra

(Beograd : Srpsko biološko društvo, 2022)

TY  - CONF
AU  - Milovanović, Jelena
AU  - Ilić, Bojan
AU  - Radulović, Niko
AU  - Mladenović, Marko
AU  - Makarov, Slobodan
AU  - Divac Rankov, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1731
AB  - Najveći broj stonoga iz klase Diplopoda poseduje hemijsku zaštitu od predatora
i/ili patogenih mikroorganizama, koji podrazumeva prisustvo odbrambenih
žlezda (ozadena) na trupu čiji se sekreti izbacuju u spoljašnju sredinu preko
otvora koji se naziva ozopora. Predstavnici reda Julida su poznati po tome da su
najčešće dominantne komponente njihovih odbrambenih sekreta hinoni. Pored
hinona, u sekretima ozadena Julida registrovani su i alkoholi, aldehidi, ketoni,
fenolna jedinjenja, kao i brojni estri zasićenih i nezasićenih karboksilnih
kiselina. Dosadašnja istraživanja su pokazala da su ekstrakti odbrambenih
sekreta Julida, kao i pojedinačna jedinjenja koja u njihov sastav ulaze, biološki
aktivni prirodni proizvodi, ali njihov citotoksični potencijal nije dovoljno
istražen. U ovoj studiji je ispitivan uticaj različitih estara linoleinske
kiseline (butil-, pentil-, heksil-, heptil-, oktil-, nonil-, fenetil- i 3-
fenilpropil-linoleat) detektovanih u odbrambenim sekretima stonoga
Megaphyllum bosniense i M. unilineatum na vijabilnost normalnih (BEAS-2B) i
kancerskih (A549) ćelija pluća korišćenjem MTT testa. Svi ispitivani estri su
smanjivali vijabilnost ćelija, pri čemu je postojala značajna razlika u odgovoru
kancerskih u odnosu na normalne ćelije u slučaju tri estra (heksil-, fenetil- i 3-
fenilpropil-linoleat). Iako su estri karboksilnih kiselina poznati kao malo
reaktivna jedinjenja, rezultati ove studije pokazuju da predstavnici ove klase
hemijskih jedinjenja mogu imati citotoksični potencijal.
AB  - Највећи број стонога из класе Diplopoda поседује хемијску заштиту од предатора
и/или патогених микроорганизама, који подразумева присуство одбрамбених
жлезда (озадена) на трупу чији се секрети избацују у спољашњу средину преко
отвора који се назива озопора. Представници реда Julida су познати по томе да су
најчешће доминантне компоненте њихових одбрамбених секрета хинони. Поред
хинона, у секретима озадена Julida регистровани су и алкохоли, алдехиди, кетони,
фенолна једињења, као и бројни естри засићених и незасићених карбоксилних
киселина. Досадашња истраживања су показала да су екстракти одбрамбених
секрета Julida, као и појединачна једињења која у њихов састав улазе, биолошки
активни природни производи, али њихов цитотоксични потенцијал није довољно
истражен. У овој студији је испитиван утицај различитих естара линолеинске
киселине (бутил-, пентил-, хексил-, хептил-, октил-, нонил-, фенетил- и 3-
фенилпропил-линолеат) детектованих у одбрамбеним секретима стонога
Megaphyllum bosniense и M. unilineatum на вијабилност нормалних (BEAS-2B) и
канцeрских (A549) ћелија плућа коришћењем МТТ теста. Сви испитивани естри су
смањивали вијабилност ћелија, при чему је постојала значајна разлика у одговору
канцерских у односу на нормалне ћелије у случају три естра (хексил-, фенетил- и 3-
фенилпропил-линолеат). Иако су естри карбоксилних киселина познати као мало
реактивна једињења, резултати ове студије показују да представници ове класе
хемијских једињења могу имати цитотоксични потенцијал.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Citotoksični potencijal estara linoleinske kiseline detektovanih u odbrambenim sekretima stonoga Megaphyllum bosniense i M. unilineatum (Diplopoda: Julida)
T1  - Цитотоксични потенцијал естара линолеинске киселине детектованих у одбрамбеним секретима стонога Megaphyllum bosniense и M. unilineatum (Diplopoda: Julida)
SP  - 186
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1731
ER  - 
@conference{
author = "Milovanović, Jelena and Ilić, Bojan and Radulović, Niko and Mladenović, Marko and Makarov, Slobodan and Divac Rankov, Aleksandra",
year = "2022",
abstract = "Najveći broj stonoga iz klase Diplopoda poseduje hemijsku zaštitu od predatora
i/ili patogenih mikroorganizama, koji podrazumeva prisustvo odbrambenih
žlezda (ozadena) na trupu čiji se sekreti izbacuju u spoljašnju sredinu preko
otvora koji se naziva ozopora. Predstavnici reda Julida su poznati po tome da su
najčešće dominantne komponente njihovih odbrambenih sekreta hinoni. Pored
hinona, u sekretima ozadena Julida registrovani su i alkoholi, aldehidi, ketoni,
fenolna jedinjenja, kao i brojni estri zasićenih i nezasićenih karboksilnih
kiselina. Dosadašnja istraživanja su pokazala da su ekstrakti odbrambenih
sekreta Julida, kao i pojedinačna jedinjenja koja u njihov sastav ulaze, biološki
aktivni prirodni proizvodi, ali njihov citotoksični potencijal nije dovoljno
istražen. U ovoj studiji je ispitivan uticaj različitih estara linoleinske
kiseline (butil-, pentil-, heksil-, heptil-, oktil-, nonil-, fenetil- i 3-
fenilpropil-linoleat) detektovanih u odbrambenim sekretima stonoga
Megaphyllum bosniense i M. unilineatum na vijabilnost normalnih (BEAS-2B) i
kancerskih (A549) ćelija pluća korišćenjem MTT testa. Svi ispitivani estri su
smanjivali vijabilnost ćelija, pri čemu je postojala značajna razlika u odgovoru
kancerskih u odnosu na normalne ćelije u slučaju tri estra (heksil-, fenetil- i 3-
fenilpropil-linoleat). Iako su estri karboksilnih kiselina poznati kao malo
reaktivna jedinjenja, rezultati ove studije pokazuju da predstavnici ove klase
hemijskih jedinjenja mogu imati citotoksični potencijal., Највећи број стонога из класе Diplopoda поседује хемијску заштиту од предатора
и/или патогених микроорганизама, који подразумева присуство одбрамбених
жлезда (озадена) на трупу чији се секрети избацују у спољашњу средину преко
отвора који се назива озопора. Представници реда Julida су познати по томе да су
најчешће доминантне компоненте њихових одбрамбених секрета хинони. Поред
хинона, у секретима озадена Julida регистровани су и алкохоли, алдехиди, кетони,
фенолна једињења, као и бројни естри засићених и незасићених карбоксилних
киселина. Досадашња истраживања су показала да су екстракти одбрамбених
секрета Julida, као и појединачна једињења која у њихов састав улазе, биолошки
активни природни производи, али њихов цитотоксични потенцијал није довољно
истражен. У овој студији је испитиван утицај различитих естара линолеинске
киселине (бутил-, пентил-, хексил-, хептил-, октил-, нонил-, фенетил- и 3-
фенилпропил-линолеат) детектованих у одбрамбеним секретима стонога
Megaphyllum bosniense и M. unilineatum на вијабилност нормалних (BEAS-2B) и
канцeрских (A549) ћелија плућа коришћењем МТТ теста. Сви испитивани естри су
смањивали вијабилност ћелија, при чему је постојала значајна разлика у одговору
канцерских у односу на нормалне ћелије у случају три естра (хексил-, фенетил- и 3-
фенилпропил-линолеат). Иако су естри карбоксилних киселина познати као мало
реактивна једињења, резултати ове студије показују да представници ове класе
хемијских једињења могу имати цитотоксични потенцијал.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Citotoksični potencijal estara linoleinske kiseline detektovanih u odbrambenim sekretima stonoga Megaphyllum bosniense i M. unilineatum (Diplopoda: Julida), Цитотоксични потенцијал естара линолеинске киселине детектованих у одбрамбеним секретима стонога Megaphyllum bosniense и M. unilineatum (Diplopoda: Julida)",
pages = "186",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1731"
}
Milovanović, J., Ilić, B., Radulović, N., Mladenović, M., Makarov, S.,& Divac Rankov, A.. (2022). Citotoksični potencijal estara linoleinske kiseline detektovanih u odbrambenim sekretima stonoga Megaphyllum bosniense i M. unilineatum (Diplopoda: Julida). in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 186.
https://hdl.handle.net/21.15107/rcub_imagine_1731
Milovanović J, Ilić B, Radulović N, Mladenović M, Makarov S, Divac Rankov A. Citotoksični potencijal estara linoleinske kiseline detektovanih u odbrambenim sekretima stonoga Megaphyllum bosniense i M. unilineatum (Diplopoda: Julida). in Treći kongres biologa Srbije. 2022;:186.
https://hdl.handle.net/21.15107/rcub_imagine_1731 .
Milovanović, Jelena, Ilić, Bojan, Radulović, Niko, Mladenović, Marko, Makarov, Slobodan, Divac Rankov, Aleksandra, "Citotoksični potencijal estara linoleinske kiseline detektovanih u odbrambenim sekretima stonoga Megaphyllum bosniense i M. unilineatum (Diplopoda: Julida)" in Treći kongres biologa Srbije (2022):186,
https://hdl.handle.net/21.15107/rcub_imagine_1731 .

The Significance of MGMT Promoter Methylation Status in Diffuse Glioma

Jovanović, Nikola; Lazarević, Milica; Cvetković, Vladimir J.; Nikolov, Vesna; Kostić Perić, Jelena; Ugrin, Milena; Pavlović, Sonja; Mitrović, Tatjana

(2022)

TY  - JOUR
AU  - Jovanović, Nikola
AU  - Lazarević, Milica
AU  - Cvetković, Vladimir J.
AU  - Nikolov, Vesna
AU  - Kostić Perić, Jelena
AU  - Ugrin, Milena
AU  - Pavlović, Sonja
AU  - Mitrović, Tatjana
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1663
AB  - A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - The Significance of MGMT Promoter Methylation Status in Diffuse Glioma
IS  - 21
SP  - 13034
VL  - 23
DO  - 10.3390/ijms232113034
ER  - 
@article{
author = "Jovanović, Nikola and Lazarević, Milica and Cvetković, Vladimir J. and Nikolov, Vesna and Kostić Perić, Jelena and Ugrin, Milena and Pavlović, Sonja and Mitrović, Tatjana",
year = "2022",
abstract = "A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "The Significance of MGMT Promoter Methylation Status in Diffuse Glioma",
number = "21",
pages = "13034",
volume = "23",
doi = "10.3390/ijms232113034"
}
Jovanović, N., Lazarević, M., Cvetković, V. J., Nikolov, V., Kostić Perić, J., Ugrin, M., Pavlović, S.,& Mitrović, T.. (2022). The Significance of MGMT Promoter Methylation Status in Diffuse Glioma. in International Journal of Molecular Sciences, 23(21), 13034.
https://doi.org/10.3390/ijms232113034
Jovanović N, Lazarević M, Cvetković VJ, Nikolov V, Kostić Perić J, Ugrin M, Pavlović S, Mitrović T. The Significance of MGMT Promoter Methylation Status in Diffuse Glioma. in International Journal of Molecular Sciences. 2022;23(21):13034.
doi:10.3390/ijms232113034 .
Jovanović, Nikola, Lazarević, Milica, Cvetković, Vladimir J., Nikolov, Vesna, Kostić Perić, Jelena, Ugrin, Milena, Pavlović, Sonja, Mitrović, Tatjana, "The Significance of MGMT Promoter Methylation Status in Diffuse Glioma" in International Journal of Molecular Sciences, 23, no. 21 (2022):13034,
https://doi.org/10.3390/ijms232113034 . .
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