Genotoxic activity of 1,2,3-triazolyl modified furocoumarins and 2,3-dihydrofurocoumarins

Genotoxic activity of 1,2,3-triazolyl modified furocoumarins and 2,3-dihydrofurocoumarins Full article

Journal

Journal of Biochemical and Molecular Toxicology
ISSN: 1095-6670 , E-ISSN: 1099-0461

Output data

Year: 2019, Volume: 33, Number: 11, Article number : e22396, Pages count : DOI: 10.1002/jbt.22396

Tags

crosslinking of DNA; furocoumarins; genotoxicity; mutagenicity; peucedanin

Authors

Kremis Stepan A. ¹ , Baev Dmitry S. ^2,3 , Lipeeva Alla, V ³ , Shults Elvira E. ^2,3 , Tolstikova Tatiana G. ^2,3 , Sinitsyna Olga, I ^2,4 , Kochetov Alexey, V ^2,4 , Frolova Tatiana S. ^1,3,4

Affiliations

1	(Данные Web of science) Fed Res Ctr Fundamental & Translat Med SB RAS, 2 Timakov St, Novosibirsk 630117, Russia
2	(Данные Web of science) Novosibirsk State Univ, Novosibirsk, Russia
3	(Данные Web of science) Novosibirsk Inst Organ Chem SB RAS, Novosibirsk, Russia
4	(Данные Web of science) Fed Res Ctr Inst Cytol & Genet SB RAS, Novosibirsk, Russia

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.

Kremis S.A. , Baev D.S. , Lipeeva A.V. , Shults E.E. , Tolstikova T.G. , Sinitsyna O.I. , Kochetov A.V. , Frolova T.S.
Genotoxic activity of 1,2,3-triazolyl modified furocoumarins and 2,3-dihydrofurocoumarins
Journal of Biochemical and Molecular Toxicology. 2019. V.33. N11. e22396 . DOI: 10.1002/jbt.22396 WOS Scopus РИНЦ

Published online:	Sep 26, 2019
Published print:	Nov 1, 2019

Web of science	WOS:000494746400006
Scopus	2-s2.0-85073989138
Elibrary	41815503
OpenAlex	W2974965166