Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels
Само за регистроване кориснике
2019
Аутори
Janković, Nenad Ž.Trifunović Ristovski, Jovana
Vraneš, Milan
Tot, Aleksandar
Petronijević, Jelena
Joksimović, Nenad
Stanojković, Tatjana P.
Đorđić Crnogorac, Marija
Petrović, Nina
Boljević, Ivana
Matić, Ivana Z.
Bogdanović, Goran A.
Mikov, Momir
Bugarčić, Zorica M.
Чланак у часопису (Објављена верзија)
,
© 2019 Elsevier Inc
Метаподаци
Приказ свих података о документуАпстракт
In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chroma...tography. © 2019 Elsevier Inc.
Кључне речи:
Biginelli scaffold / Selectivity index / Apoptosis / Caspase-9 / LipophilicityИзвор:
Bioorganic Chemistry, 2019, 86, 569-582Финансирање / пројекти:
- Испитивање механизма реакција комплекса јона прелазних метала са биолошки значајним молекулима (RS-172011)
- Интеракције ксенобиотика и утицај на системе у биомедицини (RS-41012)
DOI: 10.1016/j.bioorg.2019.02.026
ISSN: 0045-2068
WoS: 000464108100059
Scopus: 2-s2.0-85061741311
URI
https://linkinghub.elsevier.com/retrieve/pii/S0045206818312598https://vinar.vin.bg.ac.rs/handle/123456789/8071
Колекције
Институција/група
VinčaTY - JOUR AU - Janković, Nenad Ž. AU - Trifunović Ristovski, Jovana AU - Vraneš, Milan AU - Tot, Aleksandar AU - Petronijević, Jelena AU - Joksimović, Nenad AU - Stanojković, Tatjana P. AU - Đorđić Crnogorac, Marija AU - Petrović, Nina AU - Boljević, Ivana AU - Matić, Ivana Z. AU - Bogdanović, Goran A. AU - Mikov, Momir AU - Bugarčić, Zorica M. PY - 2019 UR - https://linkinghub.elsevier.com/retrieve/pii/S0045206818312598 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8071 AB - In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography. © 2019 Elsevier Inc. T2 - Bioorganic Chemistry T1 - Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels VL - 86 SP - 569 EP - 582 DO - 10.1016/j.bioorg.2019.02.026 ER -
@article{ author = "Janković, Nenad Ž. and Trifunović Ristovski, Jovana and Vraneš, Milan and Tot, Aleksandar and Petronijević, Jelena and Joksimović, Nenad and Stanojković, Tatjana P. and Đorđić Crnogorac, Marija and Petrović, Nina and Boljević, Ivana and Matić, Ivana Z. and Bogdanović, Goran A. and Mikov, Momir and Bugarčić, Zorica M.", year = "2019", abstract = "In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography. © 2019 Elsevier Inc.", journal = "Bioorganic Chemistry", title = "Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels", volume = "86", pages = "569-582", doi = "10.1016/j.bioorg.2019.02.026" }
Janković, N. Ž., Trifunović Ristovski, J., Vraneš, M., Tot, A., Petronijević, J., Joksimović, N., Stanojković, T. P., Đorđić Crnogorac, M., Petrović, N., Boljević, I., Matić, I. Z., Bogdanović, G. A., Mikov, M.,& Bugarčić, Z. M.. (2019). Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels. in Bioorganic Chemistry, 86, 569-582. https://doi.org/10.1016/j.bioorg.2019.02.026
Janković NŽ, Trifunović Ristovski J, Vraneš M, Tot A, Petronijević J, Joksimović N, Stanojković TP, Đorđić Crnogorac M, Petrović N, Boljević I, Matić IZ, Bogdanović GA, Mikov M, Bugarčić ZM. Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels. in Bioorganic Chemistry. 2019;86:569-582. doi:10.1016/j.bioorg.2019.02.026 .
Janković, Nenad Ž., Trifunović Ristovski, Jovana, Vraneš, Milan, Tot, Aleksandar, Petronijević, Jelena, Joksimović, Nenad, Stanojković, Tatjana P., Đorđić Crnogorac, Marija, Petrović, Nina, Boljević, Ivana, Matić, Ivana Z., Bogdanović, Goran A., Mikov, Momir, Bugarčić, Zorica M., "Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels" in Bioorganic Chemistry, 86 (2019):569-582, https://doi.org/10.1016/j.bioorg.2019.02.026 . .