Inhibitory Effect of New Semisynthetic Usnic Acid Derivatives on Human Tyrosyl-DNA Phosphodiesterase 1

Inhibitory Effect of New Semisynthetic Usnic Acid Derivatives on Human Tyrosyl-DNA Phosphodiesterase 1 Full article

Journal

Planta Medica
ISSN: 0032-0943 , E-ISSN: 1439-0221

Output data

Year: 2019, Volume: 85, Number: 2, Pages: 103-111 Pages count : 9 DOI: 10.1055/a-0681-7069

Tags

Usneaceae; Usnea barbata; usnic acid; terpenophenols; tyrosyl-DNA phosphodiesterase 1; Tdp1 inhibitor

Authors

Dyrkheeva Nadezhda ¹ , Luzina Olga ² , Filimonov Aleksandr ^2,3 , Zakharova Olga ¹ , Ilina Ekaterina ¹ , Zakharenko Alexandra ¹ , Kuprushkin Maxim ¹ , Nilov Dmitry ⁴ , Gushchina Irina ⁵ , Svedas Vytas ^4,5 , Salakhutdinov Nariman ^2,3 , Lavrik Olga ^1,3

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, 8 Lavrentiev Ave, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk, Russia
3	(Данные Web of science) Novosibirsk State Univ, Novosibirsk, Russia
4	(Данные Web of science) Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia
5	(Данные Web of science) Lomonosov Moscow State Univ, Fac Bioengn & Bioinformat, Moscow, Russia

Usnic acid, a lichen secondary metabolite produced by a whole number of lichens, has attracted the interest of researchers owing to its broad range of biological activity, including antiviral, antibiotic, anticancer properties, and it possessing a certain toxicity. The synthesis of new usnic acid derivatives and the investigation of their biological activity may lead to the discovery of compounds with better pharmacological and toxicity profiles. In this context, a series of new usnic acid derivatives comprising a terpenoid moiety were synthesized, and their ability to inhibit the catalytic activity of the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 was investigated. The most potent compounds (15a, 15b, 15g, and 16a, 16b, 16g) had IC50 values in the range of 0.33-2.7 mu M. The inhibitory properties were mainly dependent on the flexibility and length of the terpenoid moiety, but not strongly dependent on the configuration of the asymmetric centers. The synthesized derivatives showed low cytotoxicity against human cell lines in an MTT assay. They could be used as a basis for the development of more effective anticancer therapies when combined with topoisomerase 1 inhibitors.

Dyrkheeva N. , Luzina O. , Filimonov A. , Zakharova O. , Ilina E. , Zakharenko A. , Kuprushkin M. , Nilov D. , Gushchina I. , Svedas V. , Salakhutdinov N. , Lavrik O.
Inhibitory Effect of New Semisynthetic Usnic Acid Derivatives on Human Tyrosyl-DNA Phosphodiesterase 1
Planta Medica. 2019. V.85. N2. P.103-111. DOI: 10.1055/a-0681-7069 WOS Scopus РИНЦ OpenAlex

Published online:	Aug 24, 2018
Published print:	Jan 1, 2019

Web of science:	WOS:000458804200003
Scopus:	2-s2.0-85060375336
Elibrary:	38706465
OpenAlex:	W2888752079

DB	Citing
Web of science	13
Scopus	15
Elibrary	15
OpenAlex	16