Research output: Contribution to journal › Article › peer-review
Genotoxic activity of 1,2,3-triazolyl modified furocoumarins and 2,3-dihydrofurocoumarins. / Kremis, Stepan A.; Baev, Dmitry S.; Lipeeva, Alla V. et al.
In: Journal of Biochemical and Molecular Toxicology, Vol. 33, No. 11, e22396, 01.11.2019, p. e22396.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Genotoxic activity of 1,2,3-triazolyl modified furocoumarins and 2,3-dihydrofurocoumarins
AU - Kremis, Stepan A.
AU - Baev, Dmitry S.
AU - Lipeeva, Alla V.
AU - Shults, Elvira E.
AU - Tolstikova, Tatiana G.
AU - Sinitsyna, Olga I.
AU - Kochetov, Alexey V.
AU - Frolova, Tatiana S.
N1 - Publisher Copyright: © 2019 Wiley Periodicals, Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - crosslinking of DNA
KW - furocoumarins
KW - genotoxicity
KW - mutagenicity
KW - peucedanin
KW - ASSAY
KW - DNA-DAMAGE
KW - PSORALEN
UR - http://www.scopus.com/inward/record.url?scp=85073989138&partnerID=8YFLogxK
U2 - 10.1002/jbt.22396
DO - 10.1002/jbt.22396
M3 - Article
C2 - 31557364
AN - SCOPUS:85073989138
VL - 33
SP - e22396
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
SN - 1095-6670
IS - 11
M1 - e22396
ER -
ID: 21993243