4.5 Article

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

期刊

PLANTA MEDICA
卷 85, 期 2, 页码 103-111

出版社

GEORG THIEME VERLAG KG
DOI: 10.1055/a-0681-7069

关键词

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

资金

  1. Russian State funded budget project [VI.57.1.2, 0309-2016-0001]
  2. Russian Foundation for Basic Research [16-03-00374, 16-34-01219, 17-04-01071]

向作者/读者索取更多资源

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.

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