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Genotoxic activity of 1,2,3‐triazolyl modified furocoumarins and 2,3‐dihydrofurocoumarins
Author(s) -
Kremis Stepan A.,
Baev Dmitry S.,
Lipeeva Alla V.,
Shults Elvira E.,
Tolstikova Tatiana G.,
Sinitsyna Olga I.,
Kochetov Alexey V.,
Frolova Tatiana S.
Publication year - 2019
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22396
Subject(s) - furocoumarins , furocoumarin , chemistry , dna , combinatorial chemistry , stacking , stereochemistry , biochemistry , organic chemistry , photochemistry
The furocoumarin backbone is a promising platform for chemical modifications aimed at creating new pharmaceutical agents. However, the high level of biological activity of furocoumarins is associated with a number of negative effects. For example, some of the naturally occurring ones and their derivatives can show genotoxic and mutagenic properties as a result of their forming crosslinks with DNA molecules. Therefore, a particularly important area for the chemical modification of natural furocoumarins is to reduce the negative aspects of their bioactivity. By studying a group of 21 compounds—1,2,3‐triazolyl modified derivatives of furocoumarin and peucedanin—using the SOS chromotest, the Ames test, and DNA‐comet assays, we revealed modifications that can neutralize the structure's genotoxic properties. Theoretical aspects of the interaction of the compound library were studied using molecular modeling and this identified the leading role of the polyaromatic molecular core that takes part in stacking‐interactions with the pi‐systems of the nitrogenous bases of DNA.