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 . .