TY  - JOUR
AU  - Karagüzel, Ayşe
AU  - Uğur, Sümeyye Buran
AU  - Çetinkaya, Yasin
AU  - Doğan, Şengül Dilem
AU  - Stevanović, Milena
AU  - Nikodinović-Runić, Jasmina
AU  - Gündüz, Miyase Gözde
PY  - 2024
UR  - https://www.sciencedirect.com/science/article/pii/S0022286024003107
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2317
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate inflammation and pain through the inhibition of cyclooxygenase (COX) enzymes. Besides these widely recognized therapeutic utilizations, NSAIDs have been reported to display moderate antimicrobial activity and enhance antimicrobial efficacy when administered in combination with commercial antimicrobial drugs. In the present study, we designed novel potential antimicrobial agents by linking some NSAIDs (ibuprofen, flurbiprofen, and naproxen) to various azole rings (pyrazole, imidazole, triazole, and benzimidazole) via hydrazone functionality. The hydrazone linker was introduced into the chemical scaffold of the title molecules by the reaction between hydrazides obtained from NSAIDs and in-house synthesized azole-carrying benzaldehydes. The structures of the target compounds were elucidated by a combination of spectral methods. The NOESY spectra and stereochemical analyses performed using DFT method confirmed the presence of the target molecules as a mixture of E(C=N)-E(N-N)-synperiplanar and E(C=N)-E(N-N)-antiperiplanar conformers in DMSO-d6 solution. 1H and 13C NMR chemical shift values in DMSO were calculated using the GIAO method and compared with the experimental NMR data. Finally, some derivatives were demonstrated to inhibit Candida albicans filamentation and/or bacterial communication system known as quorum sensing. For COX inhibitor-azole hybrids with antimicrobial potency, naproxen appeared to be the most appropriate NSAID, while bulky benzimidazole was not found as a preferable azole ring.
PB  - Elsevier
T2  - Journal of Molecular Structure
T2  - Journal of Molecular StructureJournal of Molecular Structure
T1  - Azole rings linked to COX inhibitors via hydrazone bridge: Synthesis, stereochemical analysis, and investigation of antimicrobial activity
SP  - 137787
DO  - 10.1016/j.molstruc.2024.137787
ER  - 

@article{
author = "Karagüzel, Ayşe and Uğur, Sümeyye Buran and Çetinkaya, Yasin and Doğan, Şengül Dilem and Stevanović, Milena and Nikodinović-Runić, Jasmina and Gündüz, Miyase Gözde",
year = "2024",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate inflammation and pain through the inhibition of cyclooxygenase (COX) enzymes. Besides these widely recognized therapeutic utilizations, NSAIDs have been reported to display moderate antimicrobial activity and enhance antimicrobial efficacy when administered in combination with commercial antimicrobial drugs. In the present study, we designed novel potential antimicrobial agents by linking some NSAIDs (ibuprofen, flurbiprofen, and naproxen) to various azole rings (pyrazole, imidazole, triazole, and benzimidazole) via hydrazone functionality. The hydrazone linker was introduced into the chemical scaffold of the title molecules by the reaction between hydrazides obtained from NSAIDs and in-house synthesized azole-carrying benzaldehydes. The structures of the target compounds were elucidated by a combination of spectral methods. The NOESY spectra and stereochemical analyses performed using DFT method confirmed the presence of the target molecules as a mixture of E(C=N)-E(N-N)-synperiplanar and E(C=N)-E(N-N)-antiperiplanar conformers in DMSO-d6 solution. 1H and 13C NMR chemical shift values in DMSO were calculated using the GIAO method and compared with the experimental NMR data. Finally, some derivatives were demonstrated to inhibit Candida albicans filamentation and/or bacterial communication system known as quorum sensing. For COX inhibitor-azole hybrids with antimicrobial potency, naproxen appeared to be the most appropriate NSAID, while bulky benzimidazole was not found as a preferable azole ring.",
publisher = "Elsevier",
journal = "Journal of Molecular Structure, Journal of Molecular StructureJournal of Molecular Structure",
title = "Azole rings linked to COX inhibitors via hydrazone bridge: Synthesis, stereochemical analysis, and investigation of antimicrobial activity",
pages = "137787",
doi = "10.1016/j.molstruc.2024.137787"
}

Karagüzel, A., Uğur, S. B., Çetinkaya, Y., Doğan, Ş. D., Stevanović, M., Nikodinović-Runić, J.,& Gündüz, M. G.. (2024). Azole rings linked to COX inhibitors via hydrazone bridge: Synthesis, stereochemical analysis, and investigation of antimicrobial activity. in Journal of Molecular Structure
Elsevier., 137787.
https://doi.org/10.1016/j.molstruc.2024.137787

Karagüzel A, Uğur SB, Çetinkaya Y, Doğan ŞD, Stevanović M, Nikodinović-Runić J, Gündüz MG. Azole rings linked to COX inhibitors via hydrazone bridge: Synthesis, stereochemical analysis, and investigation of antimicrobial activity. in Journal of Molecular Structure. 2024;:137787.
doi:10.1016/j.molstruc.2024.137787 .

Karagüzel, Ayşe, Uğur, Sümeyye Buran, Çetinkaya, Yasin, Doğan, Şengül Dilem, Stevanović, Milena, Nikodinović-Runić, Jasmina, Gündüz, Miyase Gözde, "Azole rings linked to COX inhibitors via hydrazone bridge: Synthesis, stereochemical analysis, and investigation of antimicrobial activity" in Journal of Molecular Structure (2024):137787,
https://doi.org/10.1016/j.molstruc.2024.137787 . .

TY  - JOUR
AU  - Özcan, Esma
AU  - Vagolu, Siva Krishna
AU  - Gündüz, Miyase Gözde
AU  - Stevanović, Milena
AU  - Kökbudak, Zülbiye
AU  - Tønjum, Tone
AU  - Nikodinović-Runić, Jasmina
AU  - Çetinkaya, Yasin
AU  - Doğan, Şengül Dilem
PY  - 2023
UR  - https://doi.org/10.1021/acsomega.3c03018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2154
AB  - The discovery of new antimicrobial agents as a means of treating drug-resistant microbial pathogens is of utmost significance to overcome their immense risk to human well-being. The current investigation involves the development, synthesis, and assessment of the antimicrobial efficacy of novel quinoline derivatives incorporating a thiosemicarbazide functionality. To design the target compounds (QST1–QST14), we applied the molecular hybridization approach to link various thiosemicarbazides to the quinoline core with a sulfonyl group. Upon the synthesis and completion of structural characterization via spectroscopic techniques (1H NMR, 13C NMR, 15N NMR, IR, and HRMS), the title molecules were extensively evaluated for their potential antitubercular, antibacterial, and antifungal activities. N-(3-Chlorophenyl)-2-(quinolin-8-ylsulfonyl)hydrazine-1-carbothioamide (QST4), the most effective compound against Mycobacterium tuberculosis H37Rv, was also tested on isoniazid-resistant clinical isolates with katG and inhA promoter mutations. Based on molecular docking studies, QST4 was also likely to demonstrate its antimycobacterial activity through inhibition of the InhA enzyme. Furthermore, three derivatives (QST3, QST4, and QST10) with preferable antimicrobial and drug-like profiles were also shown to be nontoxic against human embryonic kidney (HEK) cells. All compounds were optimized by the density functional theory method using B3LYP with the 6-31+G(d,p) basis set. Structural analysis, natural bond orbital calculations of donor–acceptor interactions, molecular electrostatic potential analysis, and frontier molecular orbital analysis were carried out. Quantum chemical descriptors and charges on the atoms were determined to compare the strengths of the intramolecular hydrogen bonds formed and their stabilities. We determined that the sulfur atom forms a stronger intramolecular hydrogen bond than the nitrogen, oxygen, and fluorine atoms in these sulfonyl thiosemicarbazide derivatives.
T2  - ACS Omega
T1  - Novel Quinoline-Based Thiosemicarbazide Derivatives: Synthesis, DFT Calculations, and Investigation of Antitubercular, Antibacterial, and Antifungal Activities
EP  - 40152
IS  - 43
SP  - 40140
VL  - 8
DO  - 10.1021/acsomega.3c03018
ER  - 

@article{
author = "Özcan, Esma and Vagolu, Siva Krishna and Gündüz, Miyase Gözde and Stevanović, Milena and Kökbudak, Zülbiye and Tønjum, Tone and Nikodinović-Runić, Jasmina and Çetinkaya, Yasin and Doğan, Şengül Dilem",
year = "2023",
abstract = "The discovery of new antimicrobial agents as a means of treating drug-resistant microbial pathogens is of utmost significance to overcome their immense risk to human well-being. The current investigation involves the development, synthesis, and assessment of the antimicrobial efficacy of novel quinoline derivatives incorporating a thiosemicarbazide functionality. To design the target compounds (QST1–QST14), we applied the molecular hybridization approach to link various thiosemicarbazides to the quinoline core with a sulfonyl group. Upon the synthesis and completion of structural characterization via spectroscopic techniques (1H NMR, 13C NMR, 15N NMR, IR, and HRMS), the title molecules were extensively evaluated for their potential antitubercular, antibacterial, and antifungal activities. N-(3-Chlorophenyl)-2-(quinolin-8-ylsulfonyl)hydrazine-1-carbothioamide (QST4), the most effective compound against Mycobacterium tuberculosis H37Rv, was also tested on isoniazid-resistant clinical isolates with katG and inhA promoter mutations. Based on molecular docking studies, QST4 was also likely to demonstrate its antimycobacterial activity through inhibition of the InhA enzyme. Furthermore, three derivatives (QST3, QST4, and QST10) with preferable antimicrobial and drug-like profiles were also shown to be nontoxic against human embryonic kidney (HEK) cells. All compounds were optimized by the density functional theory method using B3LYP with the 6-31+G(d,p) basis set. Structural analysis, natural bond orbital calculations of donor–acceptor interactions, molecular electrostatic potential analysis, and frontier molecular orbital analysis were carried out. Quantum chemical descriptors and charges on the atoms were determined to compare the strengths of the intramolecular hydrogen bonds formed and their stabilities. We determined that the sulfur atom forms a stronger intramolecular hydrogen bond than the nitrogen, oxygen, and fluorine atoms in these sulfonyl thiosemicarbazide derivatives.",
journal = "ACS Omega",
title = "Novel Quinoline-Based Thiosemicarbazide Derivatives: Synthesis, DFT Calculations, and Investigation of Antitubercular, Antibacterial, and Antifungal Activities",
pages = "40152-40140",
number = "43",
volume = "8",
doi = "10.1021/acsomega.3c03018"
}

Özcan, E., Vagolu, S. K., Gündüz, M. G., Stevanović, M., Kökbudak, Z., Tønjum, T., Nikodinović-Runić, J., Çetinkaya, Y.,& Doğan, Ş. D.. (2023). Novel Quinoline-Based Thiosemicarbazide Derivatives: Synthesis, DFT Calculations, and Investigation of Antitubercular, Antibacterial, and Antifungal Activities. in ACS Omega, 8(43), 40140-40152.
https://doi.org/10.1021/acsomega.3c03018

Özcan E, Vagolu SK, Gündüz MG, Stevanović M, Kökbudak Z, Tønjum T, Nikodinović-Runić J, Çetinkaya Y, Doğan ŞD. Novel Quinoline-Based Thiosemicarbazide Derivatives: Synthesis, DFT Calculations, and Investigation of Antitubercular, Antibacterial, and Antifungal Activities. in ACS Omega. 2023;8(43):40140-40152.
doi:10.1021/acsomega.3c03018 .

Özcan, Esma, Vagolu, Siva Krishna, Gündüz, Miyase Gözde, Stevanović, Milena, Kökbudak, Zülbiye, Tønjum, Tone, Nikodinović-Runić, Jasmina, Çetinkaya, Yasin, Doğan, Şengül Dilem, "Novel Quinoline-Based Thiosemicarbazide Derivatives: Synthesis, DFT Calculations, and Investigation of Antitubercular, Antibacterial, and Antifungal Activities" in ACS Omega, 8, no. 43 (2023):40140-40152,
https://doi.org/10.1021/acsomega.3c03018 . .

TY  - JOUR
AU  - Doğan, Şengül Dilem
AU  - Özcan, Esma
AU  - Çetinkaya, Yasin
AU  - İhsan Han, Muhammed
AU  - Şahin, Onur
AU  - Bogojević Škaro, Sanja
AU  - Nikodinović-Runić, Jasmina
AU  - Gündüz, Miyase Gözde
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0022286023012486
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1935
AB  - In the present work, we report the synthesis, structural characterization, and computational studies of (E)-N'-((5-nitrofuran-2-yl)methylene)quinoline-8-sulfonohydrazide (QNF) as a potential antimicrobial drug candidate. To design the target molecule, we utilized a molecular hybridization technique that connects two antimicrobial pharmacophores (quinoline and 5-nitrofuran rings) with a sulfonyl hydrazone moiety. QNF was synthesized by the condensation of quinoline-8-sulfonohydrazide with 5-nitrofuran-2-carbaldehyde, and characterized by various spectral techniques including single-crystal X-ray crystallography. QNF was extensively evaluated for its antibacterial and antifungal activity. The inhibition capacity of QNF on Candida albicans filamentation and biofilm formation was further investigated. Biofilm inhibition of QNF against C. albicans was supported by molecular docking studies in the binding site of agglutinin-like sequence 3 (Als3). Drug-like profile of QNF was confirmed by in silico calculation of its significant physicochemical properties. Additionally, the optimized geometrical structure, natural bond orbital calculations, frontier molecular orbital and molecular electrostatic potential analysis of QNF were carried out using the density functional theory method at the B3LYP with 6-31+G(d,p) basis set. 1H and 13C NMR chemical shift values were performed using the gauge-invariant atomic orbital method. Structural parameters and NMR values obtained experimentally were compared with the calculated values.
T2  - Journal of Molecular Structure
T1  - Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity
SP  - 136155
VL  - 1292
DO  - 10.1016/j.molstruc.2023.136155
ER  - 

@article{
author = "Doğan, Şengül Dilem and Özcan, Esma and Çetinkaya, Yasin and İhsan Han, Muhammed and Şahin, Onur and Bogojević Škaro, Sanja and Nikodinović-Runić, Jasmina and Gündüz, Miyase Gözde",
year = "2023",
abstract = "In the present work, we report the synthesis, structural characterization, and computational studies of (E)-N'-((5-nitrofuran-2-yl)methylene)quinoline-8-sulfonohydrazide (QNF) as a potential antimicrobial drug candidate. To design the target molecule, we utilized a molecular hybridization technique that connects two antimicrobial pharmacophores (quinoline and 5-nitrofuran rings) with a sulfonyl hydrazone moiety. QNF was synthesized by the condensation of quinoline-8-sulfonohydrazide with 5-nitrofuran-2-carbaldehyde, and characterized by various spectral techniques including single-crystal X-ray crystallography. QNF was extensively evaluated for its antibacterial and antifungal activity. The inhibition capacity of QNF on Candida albicans filamentation and biofilm formation was further investigated. Biofilm inhibition of QNF against C. albicans was supported by molecular docking studies in the binding site of agglutinin-like sequence 3 (Als3). Drug-like profile of QNF was confirmed by in silico calculation of its significant physicochemical properties. Additionally, the optimized geometrical structure, natural bond orbital calculations, frontier molecular orbital and molecular electrostatic potential analysis of QNF were carried out using the density functional theory method at the B3LYP with 6-31+G(d,p) basis set. 1H and 13C NMR chemical shift values were performed using the gauge-invariant atomic orbital method. Structural parameters and NMR values obtained experimentally were compared with the calculated values.",
journal = "Journal of Molecular Structure",
title = "Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity",
pages = "136155",
volume = "1292",
doi = "10.1016/j.molstruc.2023.136155"
}

Doğan, Ş. D., Özcan, E., Çetinkaya, Y., İhsan Han, M., Şahin, O., Bogojević Škaro, S., Nikodinović-Runić, J.,& Gündüz, M. G.. (2023). Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity. in Journal of Molecular Structure, 1292, 136155.
https://doi.org/10.1016/j.molstruc.2023.136155

Doğan ŞD, Özcan E, Çetinkaya Y, İhsan Han M, Şahin O, Bogojević Škaro S, Nikodinović-Runić J, Gündüz MG. Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity. in Journal of Molecular Structure. 2023;1292:136155.
doi:10.1016/j.molstruc.2023.136155 .

Doğan, Şengül Dilem, Özcan, Esma, Çetinkaya, Yasin, İhsan Han, Muhammed, Şahin, Onur, Bogojević Škaro, Sanja, Nikodinović-Runić, Jasmina, Gündüz, Miyase Gözde, "Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity" in Journal of Molecular Structure, 1292 (2023):136155,
https://doi.org/10.1016/j.molstruc.2023.136155 . .