Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
Autori
Assaleh, Mohamed H.Bjelogrlić, Snežana K.
Prlainović, Nevena
Cvijetić, Ilija
Božić, Aleksandra R.
Aranđelović, Irena
Vuković, Dragana
Marinković, Aleksandar
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 af...fected 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.
Ključne reči:
Anti-cancer / Anti-mycobacterial / Cinnamic acid hydrazides / HepatotoxicityIzvor:
Arabian Journal of Chemistry, 2022, 15, 1, 103532-Izdavač:
- Elsevier
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200110 (Univerzitet u Beogradu, Medicinski fakultet) (RS-MESTD-inst-2020-200110)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200043 (Institut za onkologiju i radiologiju Srbije, Beograd) (RS-MESTD-inst-2020-200043)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200168 (Univerzitet u Beogradu, Hemijski fakultet) (RS-MESTD-inst-2020-200168)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200135 (Univerzitet u Beogradu, Tehnološko-metalurški fakultet) (RS-MESTD-inst-2020-200135)
Napomena:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/4868
DOI: 10.1016/j.arabjc.2021.103532
ISSN: 1878-5352
WoS: 000734892700004
Scopus: 2-s2.0-85118916440
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - 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 . .