Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines
Само за регистроване кориснике
2022
Аутори
Vujatović, Tamara B.Vitorović-Todorović, Maja D.
Cvijetić, Ilija
Vasović, Tamara
Nikolić, Milan
Novaković, Irena T.
Bjelogrlić, Snežana K.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In the present work, the α,β-double bond of the aroylacrylic acid phenylamides was suitably modified to optimize the toxicity–antiproliferative activity ratio of the resulting compounds 1–5. The phenylamides were modified by Michael's addition of suitably chosen piperidine-containing fragments: 1-amino-N-benzylpiperidine (a1), 4-benzylpiperidine (a2), and N,N-dimethyl-N-[2-(1-piperazinyl)-ethyl]amine (a3). The compounds exerted micromolar activity toward three cancer cell lines, A549, LoVo, and Skov-3, causing apoptotic cell death. It was shown that the nature of the cyclic amine moiety at position C2 of the compounds is probably the primary determinant of anticancer activity toward tested cell lines and the acute toxicity toward brine shrimp (Artemia salina). The majority of compounds revealed the ability to vigorously induce mitochondrial superoxide anion generation in all treated cell lines, which together with cell cycle arrest at the S phase and activation of intrinsic caspase cas...cade, indicates the possibility that apoptosis was triggered due to irreparable chromosomal damage by acute oxidative stress. Two derivatives also exerted significant antibacterial activity with one order of magnitude higher potency than chloramphenicol in most of the investigated bacterial strains. Also, the drug-like properties for all compounds were estimated by available software tools.
Кључне речи:
Antibacterial activity / Anticancer activity / Apoptosis / Aroylacrylic acid phenylamides / Michael's addition / PiperidineИзвор:
Journal of Molecular Structure, 2022, 1250, 131702-Издавач:
- Elsevier
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200168 (Универзитет у Београду, Хемијски факултет) (RS-MESTD-inst-2020-200168)
Напомена:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/4762
Повезане информације:
DOI: 10.1016/j.molstruc.2021.131702
ISSN: 0022-2860
WoS: 000718042800003
Scopus: 2-s2.0-85117959646
URI
https://www.sciencedirect.com/science/article/pii/S0022286021018287http://cherry.chem.bg.ac.rs/handle/123456789/4761
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Vujatović, Tamara B. AU - Vitorović-Todorović, Maja D. AU - Cvijetić, Ilija AU - Vasović, Tamara AU - Nikolić, Milan AU - Novaković, Irena T. AU - Bjelogrlić, Snežana K. PY - 2022 UR - https://www.sciencedirect.com/science/article/pii/S0022286021018287 UR - http://cherry.chem.bg.ac.rs/handle/123456789/4761 AB - In the present work, the α,β-double bond of the aroylacrylic acid phenylamides was suitably modified to optimize the toxicity–antiproliferative activity ratio of the resulting compounds 1–5. The phenylamides were modified by Michael's addition of suitably chosen piperidine-containing fragments: 1-amino-N-benzylpiperidine (a1), 4-benzylpiperidine (a2), and N,N-dimethyl-N-[2-(1-piperazinyl)-ethyl]amine (a3). The compounds exerted micromolar activity toward three cancer cell lines, A549, LoVo, and Skov-3, causing apoptotic cell death. It was shown that the nature of the cyclic amine moiety at position C2 of the compounds is probably the primary determinant of anticancer activity toward tested cell lines and the acute toxicity toward brine shrimp (Artemia salina). The majority of compounds revealed the ability to vigorously induce mitochondrial superoxide anion generation in all treated cell lines, which together with cell cycle arrest at the S phase and activation of intrinsic caspase cascade, indicates the possibility that apoptosis was triggered due to irreparable chromosomal damage by acute oxidative stress. Two derivatives also exerted significant antibacterial activity with one order of magnitude higher potency than chloramphenicol in most of the investigated bacterial strains. Also, the drug-like properties for all compounds were estimated by available software tools. PB - Elsevier T2 - Journal of Molecular Structure T1 - Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines VL - 1250 SP - 131702 DO - 10.1016/j.molstruc.2021.131702 ER -
@article{ author = "Vujatović, Tamara B. and Vitorović-Todorović, Maja D. and Cvijetić, Ilija and Vasović, Tamara and Nikolić, Milan and Novaković, Irena T. and Bjelogrlić, Snežana K.", year = "2022", abstract = "In the present work, the α,β-double bond of the aroylacrylic acid phenylamides was suitably modified to optimize the toxicity–antiproliferative activity ratio of the resulting compounds 1–5. The phenylamides were modified by Michael's addition of suitably chosen piperidine-containing fragments: 1-amino-N-benzylpiperidine (a1), 4-benzylpiperidine (a2), and N,N-dimethyl-N-[2-(1-piperazinyl)-ethyl]amine (a3). The compounds exerted micromolar activity toward three cancer cell lines, A549, LoVo, and Skov-3, causing apoptotic cell death. It was shown that the nature of the cyclic amine moiety at position C2 of the compounds is probably the primary determinant of anticancer activity toward tested cell lines and the acute toxicity toward brine shrimp (Artemia salina). The majority of compounds revealed the ability to vigorously induce mitochondrial superoxide anion generation in all treated cell lines, which together with cell cycle arrest at the S phase and activation of intrinsic caspase cascade, indicates the possibility that apoptosis was triggered due to irreparable chromosomal damage by acute oxidative stress. Two derivatives also exerted significant antibacterial activity with one order of magnitude higher potency than chloramphenicol in most of the investigated bacterial strains. Also, the drug-like properties for all compounds were estimated by available software tools.", publisher = "Elsevier", journal = "Journal of Molecular Structure", title = "Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines", volume = "1250", pages = "131702", doi = "10.1016/j.molstruc.2021.131702" }
Vujatović, T. B., Vitorović-Todorović, M. D., Cvijetić, I., Vasović, T., Nikolić, M., Novaković, I. T.,& Bjelogrlić, S. K.. (2022). Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines. in Journal of Molecular Structure Elsevier., 1250, 131702. https://doi.org/10.1016/j.molstruc.2021.131702
Vujatović TB, Vitorović-Todorović MD, Cvijetić I, Vasović T, Nikolić M, Novaković IT, Bjelogrlić SK. Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines. in Journal of Molecular Structure. 2022;1250:131702. doi:10.1016/j.molstruc.2021.131702 .
Vujatović, Tamara B., Vitorović-Todorović, Maja D., Cvijetić, Ilija, Vasović, Tamara, Nikolić, Milan, Novaković, Irena T., Bjelogrlić, Snežana K., "Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines" in Journal of Molecular Structure, 1250 (2022):131702, https://doi.org/10.1016/j.molstruc.2021.131702 . .