Registration Number
0224U001647,
0123U100824
, R & D reports
Title
Determining the safety of the innovative analgesic propoxazepam in its chemical and biological interactions with other drugs in polytherapy
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Head
Holovenko Mykola Ya., Доктор біологічних наук
Registration Date
26-01-2024
Organization
Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine
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The aim of the stage - Experimental study of the possible interaction of propoxazepam with other drugs in the conditions of polytherapy in order to confirm the safety of the drug. The characteristics of the crystalline state of propoxazepam were established, it was shown that molecules A and B alternately form endless chains along the [1 0 0] crystallographic direction due to intermolecular hydrogen bonds. The energy of interaction of each of the molecules with neighboring molecules in the chain is 32.9 kcal/mol. Between adjacent chains, the energy of interaction is practically equal. Propoxazepam (I) and its 3-hydroxymetabolite (II) when interacting with the CYP of the liver of rats administered phenobarbital and 3-methylcholanthrene, demonstrated the 2nd type of spectral changes of hemoprotein, which is characteristic of the binding of compounds with heme iron. Binding constants I and II differ significantly, which indicates the possibility of interaction of substrates with different sites of CYP. The obtained data indicate a possible irreversible inhibition of CYP activities by compounds I and II. Using the QSAR methodology, an in silico prediction of safe and dangerous DDIs for propoxazepam in a sample of commercially available drugs (1134 names) was performed: 267 DDIs are predicted as dangerous and 867 as safe.
Product Description
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Artemenko Anatoliy G.
Burenkova Nataliya O.
Valivodz Iryna P.
Golovenko Mykola Yakovych
Kichova Maria E.
Larionov Vitalii B.
Ohnichenko Lyudmyla M.
Khromov Oleksandr I.
Tsapenko Zhanna М.
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2024-01-26
