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

Nadezhda Dyrkheeva, Olga Luzina, Aleksandr Filimonov, Olga Zakharova, Ekaterina Ilina, Alexandra Zakharenko, Maxim Kuprushkin, Dmitry Nilov, Irina Gushchina, Vytas Švedas, Nariman Salakhutdinov, Olga Lavrik

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

9 Цитирования (Scopus)


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 IC 50 values in the range of 0.33-2.7 μM. 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.

Язык оригиналаанглийский
Страницы (с-по)103-111
Число страниц9
ЖурналPlanta Medica
Номер выпуска2
СостояниеОпубликовано - 1 янв 2019


Подробные сведения о темах исследования «Inhibitory Effect of New Semisynthetic Usnic Acid Derivatives on Human Tyrosyl-DNA Phosphodiesterase 1». Вместе они формируют уникальный семантический отпечаток (fingerprint).