Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets in silico and in vitro
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Elena I. Fedoros1,5, Alexey A. Orlov2, Alexander Zherebker2,8, Ekaterina A. Gubareva1, Mikhail A. Maydin1, Andrey I. Konstantinov2, Konstantin A. Krasnov3, Ruben N. Karapetian4, Ekaterina I. Izotova5, Sergey E. Pigarev5, Andrey V. Panchenko1, Margarita L. Tyndyk1, Dmitry I. Osolodkin6,7, Evgeny N. Nikolaev8,9,10, Irina V. Perminova2 and Vladimir N. Anisimov1
1N.N. Petrov National Medical Research Center of Oncology, Saint-Petersburg 197758, Russia
2Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia
3Institute of Toxicology, Federal Medical-Biological Agency, Saint-Petersburg 192019, Russia
4CHEMDIV LTD, Moscow District, Khimki 141400, Russia
5Nobel LTD, Saint-Petersburg 192012, Russia
6Institute of Poliomyelitis and Viral Encephalitides, Chumakov FSC R&D IBP RAS, Moscow 108819, Russia
7Sechenov First Moscow State Medical University, Moscow 119991, Russia
8Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia
9Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Moscow 119334, Russia
10Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow 119121, Russia
Vladimir N. Anisimov, email: [email protected]
Irina V. Perminova, email: [email protected]
Keywords: cancer; polyphenols; molecular targets; BP-Cx-1; ChEMBL
Received: December 15, 2017 Accepted: December 16, 2017 Published: April 06, 2018
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.
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