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 . .