Anti-Proliferative Potential of Cynaroside and Orientin—In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies
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Published:2023-11-21
Issue:23
Volume:24
Page:16555
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Pirvu Lucia Camelia1ORCID, Pintilie Lucia2ORCID, Albulescu Adrian34, Stefaniu Amalia1ORCID, Neagu Georgeta3ORCID
Affiliation:
1. Department of Pharmaceutical Biotechnologies, National Institute of Chemical Pharmaceutical R&D—ICCF Bucharest, 112 Vitan, 031299 Bucharest, Romania 2. Department of Synthesis of Bioactive Substances and Pharmaceutical Technologies, National Institute of Chemical Pharmaceutical R&D—ICCF Bucharest, 112 Vitan, 031299 Bucharest, Romania 3. Department of Pharmacology, National Institute of Chemical Pharmaceutical R&D—ICCF Bucharest, 112 Vitan, 031299 Bucharest, Romania 4. Stefan S. Nicolau Institute of Virology, Molecular Virology Department, 285 Mihai Bravu, 030304 Bucharest, Romania
Abstract
Luteolin derivates are plant compounds with multiple benefits for human health. Stability to heat and acid hydrolysis and high resistance to (auto)oxidation are other arguments for the laden interest in luteolin derivates today. The present study was designed to compare the in silico and in vitro anti-proliferative potential of two luteolin derivates, luteolin-7-O-glucoside/cynaroside (7-Lut) and luteolin-8-C-glucoside/orientin (8-Lut). In silico investigations were carried out on the molecular target, namely, the human dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) in association with its natural ligand, curcumin (PDB ID: 5ZTN), by CLC Drug Discovery Workbench v. 1.5.1. software and Molegro Virtual Docker (MVD) v. MVD 2019.7.0. software. In vitro studies were performed on two human tumor cell lines, glioblastoma (U87) and colon carcinoma (Caco-2), respectively. Altogether, docking studies have revealed 7-Lut and 8-Lut as effective inhibitors of DYRK2, even stronger than the native ligand curcumin; in vitro studies indicated the ability of both luteolin glucosides to inhibit the viability of both human tumor cell lines, up to 85% at 50 and 100 µg/mL, respectively; the most augmented cytotoxic and anti-proliferative effects were obtained for U87 exposed to 7-Lut (IC50 = 26.34 µg/mL). The results support further studies on cynaroside and orientin to create drug formulas targeting glioblastoma and colon carcinoma in humans.
Funder
“Nucleu” Program MCID
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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