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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
Authors: Janković, Nenad
Trifunović Ristovski J.
Vranes, Milan
Tot A.
Petronijević, Jelena
Joksimović N.
Stanojkovic, Tatjana
Djordjic Crnogorac, Marija
Petrovic, Nina
Boljevic, Ivana
Matic, Ivana
Bogdanovic, Goran A.
Mikov, Momir
Bugarčić Z.
Journal: Bioorganic Chemistry
Issue Date: 1-May-2019
Abstract: © 2019 Elsevier Inc. 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.
Type: Article
DOI: 10.1016/j.bioorg.2019.02.026
ISSN: 00452068
SCOPUS: 85061741311
Appears in Collections:Faculty of Science, Kragujevac
Institute for Information Technologies, Kragujevac
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