TY  - JOUR
AU  - Keskin, Selbi
AU  - Dogan, Sengul Dilem
AU  - Gunduz, Miyase Gozde
AU  - Aleksić, Ivana
AU  - Vojnović, Sandra
AU  - Lazić, Jelena
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1514
AB  - In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies.
PB  - Elsevier, Amsterdam
T2  - Journal of Molecular Structure
T1  - Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies
VL  - 1270
DO  - 10.1016/j.molstruc.2022.133936
ER  - 

@article{
author = "Keskin, Selbi and Dogan, Sengul Dilem and Gunduz, Miyase Gozde and Aleksić, Ivana and Vojnović, Sandra and Lazić, Jelena and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Molecular Structure",
title = "Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies",
volume = "1270",
doi = "10.1016/j.molstruc.2022.133936"
}

Keskin, S., Dogan, S. D., Gunduz, M. G., Aleksić, I., Vojnović, S., Lazić, J.,& Nikodinović-Runić, J.. (2022). Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies. in Journal of Molecular Structure
Elsevier, Amsterdam., 1270.
https://doi.org/10.1016/j.molstruc.2022.133936

Keskin S, Dogan SD, Gunduz MG, Aleksić I, Vojnović S, Lazić J, Nikodinović-Runić J. Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies. in Journal of Molecular Structure. 2022;1270.
doi:10.1016/j.molstruc.2022.133936 .

Keskin, Selbi, Dogan, Sengul Dilem, Gunduz, Miyase Gozde, Aleksić, Ivana, Vojnović, Sandra, Lazić, Jelena, Nikodinović-Runić, Jasmina, "Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies" in Journal of Molecular Structure, 1270 (2022),
https://doi.org/10.1016/j.molstruc.2022.133936 . .

TY  - JOUR
AU  - Gunduz, Miyase Gozde
AU  - Dengiz, Cagatay
AU  - Aslan, Ebru Kocak
AU  - Škaro Bogojević, Sanja
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1529
AB  - In the present study, we designed three novel compounds via the combination of two precious nitrogencontaining scaffolds; 1,4-dihydropyridine (DHP) and azole, in the same molecule. To synthesize the title compounds, initially, azolyl benzaldehydes were obtained through the nucleophilic aromatic substitution reaction of 4-fluorobenzaldehyde with pyrazole, imidazole or 1,2,4-triazole. Subsequently, an unsymmetrical Hantzsch reaction was applied to achieve DHP scaffold, thus the target molecules. After structural characterization, the effects of various azole rings on optical and non-linear optical (NLO) properties were investigated by computational methods. Band gaps, chemical hardness/softness, dipole moments, average polarizability, first hyperpolarizability values were computed for the target compounds at the CAM-B3LYP/6-31++G(d,p) level of theory. The comparable results confirmed the potential of DHP-azole hybrids to be utilized in NLO devices. The title molecules were further tested for their antibacterial and antifungal activities following the evaluation of their drug likeness properties. The compounds containing imidazole or triazole rings represented better antifungal properties than antibacterial activities. Molecular docking studies were performed in the catalytic site of lanosterol 14 alpha-demethylase, CYP51, from Candida albicans to explain the obtained biological results and suggest molecular modifications to endow this class of molecules with improved antifungal effects.
PB  - Elsevier, Amsterdam
T2  - Journal of Molecular Structure
T1  - Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies
VL  - 1247
DO  - 10.1016/j.molstruc.2021.131316
ER  - 

@article{
author = "Gunduz, Miyase Gozde and Dengiz, Cagatay and Aslan, Ebru Kocak and Škaro Bogojević, Sanja and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "In the present study, we designed three novel compounds via the combination of two precious nitrogencontaining scaffolds; 1,4-dihydropyridine (DHP) and azole, in the same molecule. To synthesize the title compounds, initially, azolyl benzaldehydes were obtained through the nucleophilic aromatic substitution reaction of 4-fluorobenzaldehyde with pyrazole, imidazole or 1,2,4-triazole. Subsequently, an unsymmetrical Hantzsch reaction was applied to achieve DHP scaffold, thus the target molecules. After structural characterization, the effects of various azole rings on optical and non-linear optical (NLO) properties were investigated by computational methods. Band gaps, chemical hardness/softness, dipole moments, average polarizability, first hyperpolarizability values were computed for the target compounds at the CAM-B3LYP/6-31++G(d,p) level of theory. The comparable results confirmed the potential of DHP-azole hybrids to be utilized in NLO devices. The title molecules were further tested for their antibacterial and antifungal activities following the evaluation of their drug likeness properties. The compounds containing imidazole or triazole rings represented better antifungal properties than antibacterial activities. Molecular docking studies were performed in the catalytic site of lanosterol 14 alpha-demethylase, CYP51, from Candida albicans to explain the obtained biological results and suggest molecular modifications to endow this class of molecules with improved antifungal effects.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Molecular Structure",
title = "Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies",
volume = "1247",
doi = "10.1016/j.molstruc.2021.131316"
}

Gunduz, M. G., Dengiz, C., Aslan, E. K., Škaro Bogojević, S.,& Nikodinović-Runić, J.. (2022). Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies. in Journal of Molecular Structure
Elsevier, Amsterdam., 1247.
https://doi.org/10.1016/j.molstruc.2021.131316

Gunduz MG, Dengiz C, Aslan EK, Škaro Bogojević S, Nikodinović-Runić J. Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies. in Journal of Molecular Structure. 2022;1247.
doi:10.1016/j.molstruc.2021.131316 .

Gunduz, Miyase Gozde, Dengiz, Cagatay, Aslan, Ebru Kocak, Škaro Bogojević, Sanja, Nikodinović-Runić, Jasmina, "Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies" in Journal of Molecular Structure, 1247 (2022),
https://doi.org/10.1016/j.molstruc.2021.131316 . .

TY  - JOUR
AU  - Milovanović, Jelena
AU  - Gunduz, Miyase Gozde
AU  - Zerva, Anastasia
AU  - Petković, Milos
AU  - Beskoski, Vladimir
AU  - Thomaidis, Nikolaos S.
AU  - Topakas, Evangelos
AU  - Nikodinović-Runić, Jasmina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1442
AB  - We describe herein the synthesis and laccase mediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4-DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions.
PB  - MDPI, Basel
T2  - Catalysts
T1  - Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives
IS  - 6
VL  - 11
DO  - 10.3390/catal11060727
ER  - 

@article{
author = "Milovanović, Jelena and Gunduz, Miyase Gozde and Zerva, Anastasia and Petković, Milos and Beskoski, Vladimir and Thomaidis, Nikolaos S. and Topakas, Evangelos and Nikodinović-Runić, Jasmina",
year = "2021",
abstract = "We describe herein the synthesis and laccase mediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4-DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions.",
publisher = "MDPI, Basel",
journal = "Catalysts",
title = "Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives",
number = "6",
volume = "11",
doi = "10.3390/catal11060727"
}

Milovanović, J., Gunduz, M. G., Zerva, A., Petković, M., Beskoski, V., Thomaidis, N. S., Topakas, E.,& Nikodinović-Runić, J.. (2021). Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives. in Catalysts
MDPI, Basel., 11(6).
https://doi.org/10.3390/catal11060727

Milovanović J, Gunduz MG, Zerva A, Petković M, Beskoski V, Thomaidis NS, Topakas E, Nikodinović-Runić J. Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives. in Catalysts. 2021;11(6).
doi:10.3390/catal11060727 .

Milovanović, Jelena, Gunduz, Miyase Gozde, Zerva, Anastasia, Petković, Milos, Beskoski, Vladimir, Thomaidis, Nikolaos S., Topakas, Evangelos, Nikodinović-Runić, Jasmina, "Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives" in Catalysts, 11, no. 6 (2021),
https://doi.org/10.3390/catal11060727 . .

TY  - JOUR
AU  - Meseli, Tugba
AU  - Dogan, Sengul Dilem
AU  - Gunduz, Miyase Gozde
AU  - Kokbudak, Zulbiye
AU  - Škaro Bogojević, Sanja
AU  - Noonan, Theresa
AU  - Vojnović, Sandra
AU  - Wolber, Gerhard
AU  - Nikodinović-Runić, Jasmina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1417
AB  - Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1-SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly increased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores).
PB  - Royal Soc Chemistry, Cambridge
T2  - New Journal of Chemistry
T1  - Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety
EP  - 8177
IS  - 18
SP  - 8166
VL  - 45
DO  - 10.1039/d1nj00150g
ER  - 

@article{
author = "Meseli, Tugba and Dogan, Sengul Dilem and Gunduz, Miyase Gozde and Kokbudak, Zulbiye and Škaro Bogojević, Sanja and Noonan, Theresa and Vojnović, Sandra and Wolber, Gerhard and Nikodinović-Runić, Jasmina",
year = "2021",
abstract = "Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1-SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly increased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores).",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "New Journal of Chemistry",
title = "Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety",
pages = "8177-8166",
number = "18",
volume = "45",
doi = "10.1039/d1nj00150g"
}

Meseli, T., Dogan, S. D., Gunduz, M. G., Kokbudak, Z., Škaro Bogojević, S., Noonan, T., Vojnović, S., Wolber, G.,& Nikodinović-Runić, J.. (2021). Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety. in New Journal of Chemistry
Royal Soc Chemistry, Cambridge., 45(18), 8166-8177.
https://doi.org/10.1039/d1nj00150g

Meseli T, Dogan SD, Gunduz MG, Kokbudak Z, Škaro Bogojević S, Noonan T, Vojnović S, Wolber G, Nikodinović-Runić J. Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety. in New Journal of Chemistry. 2021;45(18):8166-8177.
doi:10.1039/d1nj00150g .

Meseli, Tugba, Dogan, Sengul Dilem, Gunduz, Miyase Gozde, Kokbudak, Zulbiye, Škaro Bogojević, Sanja, Noonan, Theresa, Vojnović, Sandra, Wolber, Gerhard, Nikodinović-Runić, Jasmina, "Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety" in New Journal of Chemistry, 45, no. 18 (2021):8166-8177,
https://doi.org/10.1039/d1nj00150g . .