Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro

Fedoros, E.I.; Orlov, A.A.; Zherebker, A.; Gubareva, E.A.; Maydin, M.A.; Konstantinov, A.I.; Krasnon, K.A.; Karapetian, R.N.; Izotova, E.I.; Pigarev, S.E.; Panchenko, A.V.; Tyndyk, M.L.; Osolodkin, D.I.; Nikolaev, E.N.; Perminova, I.V.; Anisimov, V.N.

Авторы: Fedoros Elena I., Orlov Alexey A., Zherebker Alexander, Gubareva Ekaterina A., Maydin Mikhail A., Konstantinov Andrey I., Krasnon Konstantin A., Karapetian Ruben N., Izotova Ekaterina I., Pigarev Sergey E., Panchenko Andrey V., Tyndyk Margarita L., Osolodkin Dmitry I., Nikolaev Evgeny N., Perminova Irina V., Anisimov Vladimir N.
Журнал: Oncotarget
Том: 9
Год издания: 2018
Издательство: Impact Journals
Местоположение издательства: Albany, N.Y., United States
Первая страница: 18578
Последняя страница: 18593
DOI: 10.18632/oncotarget.24990
Аннотация: Identification of molecular targets and mechanism of action is always a challenge, in particular – for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties. The results of diversity assay demonstrate that BP-Cx-1 has multiple biological effects on neurotransmitters receptors, ligand-gated ion channels and transporters. Of particular importance is that the major part of identified molecular targets are involved in modulation of inflammation and immune response and might be related to tumorigenesis. Characterization of molecular composition of BP-Cx-1 with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and subsequent identification of possible active components by searching for molecular matches in silico in ChEMBL indicated polyphenolic components, nominally, flavonoids, sapogenins, phenanthrenes, as the major carriers of biological activity of BP-Cx-1. In vitro and in silico target screening yielded overlapping lists of proteins: adenosine receptors, dopamine receptor DRD4, glucocorticoid receptor, serotonin receptor 5-HT1, prostaglandin receptors, muscarinic cholinergic receptor, GABAA receptor. The pleiotropic molecular activities of polyphenolic components are beneficial in treatment of multifactorial disorders such as diseases associated with chronic inflammation and cancer.
Добавил в систему: Перминова Ирина Васильевна

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Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitroстатья