TY  - JOUR
AU  - Assaleh, Mohamed H.
AU  - Bjelogrlić, Snežana K.
AU  - Prlainović, Nevena
AU  - Cvijetić, Ilija
AU  - Božić, Aleksandra R.
AU  - Aranđelović, Irena
AU  - Vuković, Dragana
AU  - Marinković, Aleksandar
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/4867
AB  - A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrated strong anti-Mtb activity by reducing bacilli survival for>90 % in all three treated Mtb isolates, whereas isoniazid and rifampicin did not. Moreover, compound 3 didn’t affect vitality of HepG-2 cells, implying on advantageous hepatotoxicity profile compared to current therapeutic options for tuberculosis. Compounds 2a and 3b displayed as strong inducers of apoptosis in A549 cells, both activating intrinsic caspase pathway and cell cycle arrest at the G0/G1 phase. Subsequent analyses disclosed differences in their activities, where 3b has ability to induce production of mitochondrial superoxide anions, while 2a significantly inhibited cellular mobility. More importantly, 3b considerably affected viability of HepG-2 and HaCaT cells, whereas 2a had moderate impact only on the later. Molecular modeling studies indicated high permeability and good absorption through the human intestine, and moderate aqueous solubility with poor blood–brain barrier permeability. In summary, our results reveal that novel compounds 3 and 2a represent promising agents for tuberculosis and cancer treatment, respectively, indicating that further investigation needs to be performed to clarify the mechanisms of their anti-Mtb and anticancer activity.
PB  - Elsevier
T2  - Arabian Journal of Chemistry
T1  - Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
VL  - 15
IS  - 1
SP  - 103532
DO  - 10.1016/j.arabjc.2021.103532
ER  - 

@article{
author = "Assaleh, Mohamed H. and Bjelogrlić, Snežana K. and Prlainović, Nevena and Cvijetić, Ilija and Božić, Aleksandra R. and Aranđelović, Irena and Vuković, Dragana and Marinković, Aleksandar",
year = "2022",
abstract = "A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrated strong anti-Mtb activity by reducing bacilli survival for>90 % in all three treated Mtb isolates, whereas isoniazid and rifampicin did not. Moreover, compound 3 didn’t affect vitality of HepG-2 cells, implying on advantageous hepatotoxicity profile compared to current therapeutic options for tuberculosis. Compounds 2a and 3b displayed as strong inducers of apoptosis in A549 cells, both activating intrinsic caspase pathway and cell cycle arrest at the G0/G1 phase. Subsequent analyses disclosed differences in their activities, where 3b has ability to induce production of mitochondrial superoxide anions, while 2a significantly inhibited cellular mobility. More importantly, 3b considerably affected viability of HepG-2 and HaCaT cells, whereas 2a had moderate impact only on the later. Molecular modeling studies indicated high permeability and good absorption through the human intestine, and moderate aqueous solubility with poor blood–brain barrier permeability. In summary, our results reveal that novel compounds 3 and 2a represent promising agents for tuberculosis and cancer treatment, respectively, indicating that further investigation needs to be performed to clarify the mechanisms of their anti-Mtb and anticancer activity.",
publisher = "Elsevier",
journal = "Arabian Journal of Chemistry",
title = "Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile",
volume = "15",
number = "1",
pages = "103532",
doi = "10.1016/j.arabjc.2021.103532"
}

Assaleh, M. H., Bjelogrlić, S. K., Prlainović, N., Cvijetić, I., Božić, A. R., Aranđelović, I., Vuković, D.,& Marinković, A.. (2022). Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile. in Arabian Journal of Chemistry
Elsevier., 15(1), 103532.
https://doi.org/10.1016/j.arabjc.2021.103532

Assaleh MH, Bjelogrlić SK, Prlainović N, Cvijetić I, Božić AR, Aranđelović I, Vuković D, Marinković A. Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile. in Arabian Journal of Chemistry. 2022;15(1):103532.
doi:10.1016/j.arabjc.2021.103532 .

Assaleh, Mohamed H., Bjelogrlić, Snežana K., Prlainović, Nevena, Cvijetić, Ilija, Božić, Aleksandra R., Aranđelović, Irena, Vuković, Dragana, Marinković, Aleksandar, "Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile" in Arabian Journal of Chemistry, 15, no. 1 (2022):103532,
https://doi.org/10.1016/j.arabjc.2021.103532 . .

TY  - DATA
AU  - Assaleh, Mohamed H.
AU  - Bjelogrlić, Snežana K.
AU  - Prlainović, Nevena
AU  - Cvijetić, Ilija
AU  - Božić, Aleksandra R.
AU  - Aranđelović, Irena
AU  - Vuković, Dragana
AU  - Marinković, Aleksandar
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/4868
PB  - Elsevier
T2  - Arabian Journal of Chemistry
T1  - Supplementary material for the article: Assaleh, M. H.; Bjelogrlic, S. K.; Prlainovic, N.; Cvijetic, I.; Bozic, A.; Arandjelovic, I.; Vukovic, D.; Marinkovic, A. Antimycobacterial and Anticancer Activity of Newly Designed Cinnamic Acid Hydrazides with Favorable Toxicity Profile. Arabian Journal of Chemistry 2022, 15 (1), 103532. https://doi.org/10.1016/j.arabjc.2021.103532.
UR  - https://hdl.handle.net/21.15107/rcub_cherry_4868
ER  - 

@misc{
author = "Assaleh, Mohamed H. and Bjelogrlić, Snežana K. and Prlainović, Nevena and Cvijetić, Ilija and Božić, Aleksandra R. and Aranđelović, Irena and Vuković, Dragana and Marinković, Aleksandar",
year = "2022",
publisher = "Elsevier",
journal = "Arabian Journal of Chemistry",
title = "Supplementary material for the article: Assaleh, M. H.; Bjelogrlic, S. K.; Prlainovic, N.; Cvijetic, I.; Bozic, A.; Arandjelovic, I.; Vukovic, D.; Marinkovic, A. Antimycobacterial and Anticancer Activity of Newly Designed Cinnamic Acid Hydrazides with Favorable Toxicity Profile. Arabian Journal of Chemistry 2022, 15 (1), 103532. https://doi.org/10.1016/j.arabjc.2021.103532.",
url = "https://hdl.handle.net/21.15107/rcub_cherry_4868"
}

Assaleh, M. H., Bjelogrlić, S. K., Prlainović, N., Cvijetić, I., Božić, A. R., Aranđelović, I., Vuković, D.,& Marinković, A.. (2022). Supplementary material for the article: Assaleh, M. H.; Bjelogrlic, S. K.; Prlainovic, N.; Cvijetic, I.; Bozic, A.; Arandjelovic, I.; Vukovic, D.; Marinkovic, A. Antimycobacterial and Anticancer Activity of Newly Designed Cinnamic Acid Hydrazides with Favorable Toxicity Profile. Arabian Journal of Chemistry 2022, 15 (1), 103532. https://doi.org/10.1016/j.arabjc.2021.103532.. in Arabian Journal of Chemistry
Elsevier..
https://hdl.handle.net/21.15107/rcub_cherry_4868

Assaleh MH, Bjelogrlić SK, Prlainović N, Cvijetić I, Božić AR, Aranđelović I, Vuković D, Marinković A. Supplementary material for the article: Assaleh, M. H.; Bjelogrlic, S. K.; Prlainovic, N.; Cvijetic, I.; Bozic, A.; Arandjelovic, I.; Vukovic, D.; Marinkovic, A. Antimycobacterial and Anticancer Activity of Newly Designed Cinnamic Acid Hydrazides with Favorable Toxicity Profile. Arabian Journal of Chemistry 2022, 15 (1), 103532. https://doi.org/10.1016/j.arabjc.2021.103532.. in Arabian Journal of Chemistry. 2022;.
https://hdl.handle.net/21.15107/rcub_cherry_4868 .

Assaleh, Mohamed H., Bjelogrlić, Snežana K., Prlainović, Nevena, Cvijetić, Ilija, Božić, Aleksandra R., Aranđelović, Irena, Vuković, Dragana, Marinković, Aleksandar, "Supplementary material for the article: Assaleh, M. H.; Bjelogrlic, S. K.; Prlainovic, N.; Cvijetic, I.; Bozic, A.; Arandjelovic, I.; Vukovic, D.; Marinkovic, A. Antimycobacterial and Anticancer Activity of Newly Designed Cinnamic Acid Hydrazides with Favorable Toxicity Profile. Arabian Journal of Chemistry 2022, 15 (1), 103532. https://doi.org/10.1016/j.arabjc.2021.103532." in Arabian Journal of Chemistry (2022),
https://hdl.handle.net/21.15107/rcub_cherry_4868 .

TY  - JOUR
AU  - Assaleh, Mohamed H.
AU  - Božić, Aleksandra R.
AU  - Bjelogrlić, Snežana K.
AU  - Milošević, Milena D.
AU  - Simić, Milena R.
AU  - Marinković, Aleksandar
AU  - Cvijetić, Ilija
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3846
AB  - Thiocarbohydrazones (TCHs) and structurally related molecules are versatile organic compounds which exert antioxidant, anticancer, and other beneficial health effects. The combination of UV/Vis, NMR spectroscopy, and quantum chemical calculations was used to rationalize the experimentally observed increase in the radical scavenging activity upon the addition of water in DMSO solution of TCHs. Mono- and bis(salicylaldehyde) TCHs (compounds 1 and 2) undergo water-induced E-to-Z isomerization which is followed by disruption of intramolecular hydrogen bond, ground state destabilization, and 11 kcal/mol decrease in the bond dissociation enthalpy (BDE). Electron spin delocalization is more pronounced in Z-isomers of 1 and 2. On the other hand, 2-acetylpyridine TCHs (compounds 3 and 4) undergo thione-to-thiol tautomerism which also decreases the BDE and facilitates the hydrogen atom transfer to 2,2-diphenyl-1-picrylhydrazyl radical (DPPH∙). The appearance of thiolic –SH group as another reactive site toward free radicals improves the antioxidant activity of 3 and 4. The spin density of 3- and 4-thiol radicals is delocalized over the entire thiocarbohydrazide moiety compared to more localized spin of thione radicals. Additional stabilization of thiol radicals corroborates with the increased antioxidant activity. This study provides the new insights on the solution structure of TCHs, and also highlights the importance of solution structure determination when studying the structure-antioxidant relationships of isomerizable compounds.
T2  - Structural Chemistry
T1  - Water-induced isomerism of salicylaldehyde and 2-acetylpyridine mono- and bis-(thiocarbohydrazones) improves the antioxidant activity: spectroscopic and DFT study
VL  - 30
IS  - 6
SP  - 2447
EP  - 2457
DO  - 10.1007/s11224-019-01371-4
ER  - 

@article{
author = "Assaleh, Mohamed H. and Božić, Aleksandra R. and Bjelogrlić, Snežana K. and Milošević, Milena D. and Simić, Milena R. and Marinković, Aleksandar and Cvijetić, Ilija",
year = "2019",
abstract = "Thiocarbohydrazones (TCHs) and structurally related molecules are versatile organic compounds which exert antioxidant, anticancer, and other beneficial health effects. The combination of UV/Vis, NMR spectroscopy, and quantum chemical calculations was used to rationalize the experimentally observed increase in the radical scavenging activity upon the addition of water in DMSO solution of TCHs. Mono- and bis(salicylaldehyde) TCHs (compounds 1 and 2) undergo water-induced E-to-Z isomerization which is followed by disruption of intramolecular hydrogen bond, ground state destabilization, and 11 kcal/mol decrease in the bond dissociation enthalpy (BDE). Electron spin delocalization is more pronounced in Z-isomers of 1 and 2. On the other hand, 2-acetylpyridine TCHs (compounds 3 and 4) undergo thione-to-thiol tautomerism which also decreases the BDE and facilitates the hydrogen atom transfer to 2,2-diphenyl-1-picrylhydrazyl radical (DPPH∙). The appearance of thiolic –SH group as another reactive site toward free radicals improves the antioxidant activity of 3 and 4. The spin density of 3- and 4-thiol radicals is delocalized over the entire thiocarbohydrazide moiety compared to more localized spin of thione radicals. Additional stabilization of thiol radicals corroborates with the increased antioxidant activity. This study provides the new insights on the solution structure of TCHs, and also highlights the importance of solution structure determination when studying the structure-antioxidant relationships of isomerizable compounds.",
journal = "Structural Chemistry",
title = "Water-induced isomerism of salicylaldehyde and 2-acetylpyridine mono- and bis-(thiocarbohydrazones) improves the antioxidant activity: spectroscopic and DFT study",
volume = "30",
number = "6",
pages = "2447-2457",
doi = "10.1007/s11224-019-01371-4"
}

Assaleh, M. H., Božić, A. R., Bjelogrlić, S. K., Milošević, M. D., Simić, M. R., Marinković, A.,& Cvijetić, I.. (2019). Water-induced isomerism of salicylaldehyde and 2-acetylpyridine mono- and bis-(thiocarbohydrazones) improves the antioxidant activity: spectroscopic and DFT study. in Structural Chemistry, 30(6), 2447-2457.
https://doi.org/10.1007/s11224-019-01371-4

Assaleh MH, Božić AR, Bjelogrlić SK, Milošević MD, Simić MR, Marinković A, Cvijetić I. Water-induced isomerism of salicylaldehyde and 2-acetylpyridine mono- and bis-(thiocarbohydrazones) improves the antioxidant activity: spectroscopic and DFT study. in Structural Chemistry. 2019;30(6):2447-2457.
doi:10.1007/s11224-019-01371-4 .

Assaleh, Mohamed H., Božić, Aleksandra R., Bjelogrlić, Snežana K., Milošević, Milena D., Simić, Milena R., Marinković, Aleksandar, Cvijetić, Ilija, "Water-induced isomerism of salicylaldehyde and 2-acetylpyridine mono- and bis-(thiocarbohydrazones) improves the antioxidant activity: spectroscopic and DFT study" in Structural Chemistry, 30, no. 6 (2019):2447-2457,
https://doi.org/10.1007/s11224-019-01371-4 . .

TY  - DATA
AU  - Assaleh, Mohamed H.
AU  - Božić, Aleksandra R.
AU  - Bjelogrlić, Snežana K.
AU  - Milošević, Milena D.
AU  - Simić, Milena R.
AU  - Marinković, Aleksandar
AU  - Cvijetić, Ilija
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3848
T2  - Structural Chemistry
T1  - Supplementary data for the article: Assaleh, M. H.; Božić, A. R.; Bjelogrlić, S.; Milošević, M.; Simić, M.; Marinković, A. D.; Cvijetić, I. N. Water-Induced Isomerism of Salicylaldehyde and 2-Acetylpyridine Mono- and Bis-(Thiocarbohydrazones) Improves the Antioxidant Activity: Spectroscopic and DFT Study. Struct Chem 2019, 30 (6), 2447–2457. https://doi.org/10.1007/s11224-019-01371-4
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3848
ER  - 

@misc{
author = "Assaleh, Mohamed H. and Božić, Aleksandra R. and Bjelogrlić, Snežana K. and Milošević, Milena D. and Simić, Milena R. and Marinković, Aleksandar and Cvijetić, Ilija",
year = "2019",
journal = "Structural Chemistry",
title = "Supplementary data for the article: Assaleh, M. H.; Božić, A. R.; Bjelogrlić, S.; Milošević, M.; Simić, M.; Marinković, A. D.; Cvijetić, I. N. Water-Induced Isomerism of Salicylaldehyde and 2-Acetylpyridine Mono- and Bis-(Thiocarbohydrazones) Improves the Antioxidant Activity: Spectroscopic and DFT Study. Struct Chem 2019, 30 (6), 2447–2457. https://doi.org/10.1007/s11224-019-01371-4",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3848"
}

Assaleh, M. H., Božić, A. R., Bjelogrlić, S. K., Milošević, M. D., Simić, M. R., Marinković, A.,& Cvijetić, I.. (2019). Supplementary data for the article: Assaleh, M. H.; Božić, A. R.; Bjelogrlić, S.; Milošević, M.; Simić, M.; Marinković, A. D.; Cvijetić, I. N. Water-Induced Isomerism of Salicylaldehyde and 2-Acetylpyridine Mono- and Bis-(Thiocarbohydrazones) Improves the Antioxidant Activity: Spectroscopic and DFT Study. Struct Chem 2019, 30 (6), 2447–2457. https://doi.org/10.1007/s11224-019-01371-4. in Structural Chemistry.
https://hdl.handle.net/21.15107/rcub_cherry_3848

Assaleh MH, Božić AR, Bjelogrlić SK, Milošević MD, Simić MR, Marinković A, Cvijetić I. Supplementary data for the article: Assaleh, M. H.; Božić, A. R.; Bjelogrlić, S.; Milošević, M.; Simić, M.; Marinković, A. D.; Cvijetić, I. N. Water-Induced Isomerism of Salicylaldehyde and 2-Acetylpyridine Mono- and Bis-(Thiocarbohydrazones) Improves the Antioxidant Activity: Spectroscopic and DFT Study. Struct Chem 2019, 30 (6), 2447–2457. https://doi.org/10.1007/s11224-019-01371-4. in Structural Chemistry. 2019;.
https://hdl.handle.net/21.15107/rcub_cherry_3848 .

Assaleh, Mohamed H., Božić, Aleksandra R., Bjelogrlić, Snežana K., Milošević, Milena D., Simić, Milena R., Marinković, Aleksandar, Cvijetić, Ilija, "Supplementary data for the article: Assaleh, M. H.; Božić, A. R.; Bjelogrlić, S.; Milošević, M.; Simić, M.; Marinković, A. D.; Cvijetić, I. N. Water-Induced Isomerism of Salicylaldehyde and 2-Acetylpyridine Mono- and Bis-(Thiocarbohydrazones) Improves the Antioxidant Activity: Spectroscopic and DFT Study. Struct Chem 2019, 30 (6), 2447–2457. https://doi.org/10.1007/s11224-019-01371-4" in Structural Chemistry (2019),
https://hdl.handle.net/21.15107/rcub_cherry_3848 .