In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens
Abstract
Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present pa-per, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospi-tals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) -an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, H-1 and C-13 NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic... acids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 mu M for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 10 7 and 10 9 . The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics.
Keywords:
Thiocarbohydrazones / Cinnamic acid amides / Antimicrobial activity / Acinetobacter baumannii / 3D QSARSource:
Journal of Molecular Structure, 2022, 1262Publisher:
- Elsevier, Amsterdam
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200135 (University of Belgrade, Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200135)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
DOI: 10.1016/j.molstruc.2022.133016
ISSN: 0022-2860
WoS: 000803850600010
Scopus: 2-s2.0-85128382542
Collections
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Assaleh, Mohamed H. AU - Jeremić, Sanja AU - Cvijeti, Ilija AU - Marinkovi, Aleksandar AU - Prlainovi, Nevena PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1601 AB - Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present pa-per, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospi-tals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) -an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, H-1 and C-13 NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic acids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 mu M for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 10 7 and 10 9 . The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics. PB - Elsevier, Amsterdam T2 - Journal of Molecular Structure T1 - In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens VL - 1262 DO - 10.1016/j.molstruc.2022.133016 ER -
@article{ author = "Assaleh, Mohamed H. and Jeremić, Sanja and Cvijeti, Ilija and Marinkovi, Aleksandar and Prlainovi, Nevena", year = "2022", abstract = "Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present pa-per, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospi-tals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) -an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, H-1 and C-13 NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic acids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 mu M for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 10 7 and 10 9 . The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics.", publisher = "Elsevier, Amsterdam", journal = "Journal of Molecular Structure", title = "In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens", volume = "1262", doi = "10.1016/j.molstruc.2022.133016" }
Assaleh, M. H., Jeremić, S., Cvijeti, I., Marinkovi, A.,& Prlainovi, N.. (2022). In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens. in Journal of Molecular Structure Elsevier, Amsterdam., 1262. https://doi.org/10.1016/j.molstruc.2022.133016
Assaleh MH, Jeremić S, Cvijeti I, Marinkovi A, Prlainovi N. In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens. in Journal of Molecular Structure. 2022;1262. doi:10.1016/j.molstruc.2022.133016 .
Assaleh, Mohamed H., Jeremić, Sanja, Cvijeti, Ilija, Marinkovi, Aleksandar, Prlainovi, Nevena, "In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens" in Journal of Molecular Structure, 1262 (2022), https://doi.org/10.1016/j.molstruc.2022.133016 . .