English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

We present binding modes of newly synthesized benz[f]indole-4,9-dione analogs with topoisomerase I (TOP1)-DNA complex. The compounds were tested for cytotoxicity and TOP1 inhibitory activity in our previous study. Camptothecin (CPT) and each of the 15 analogs were docked into the X-ray crystal structure of human TOP1-DNA binary complex to develop the ternary complex of TOP1-DNA-ligand using FlexiDock. The results demonstrated that two compounds with N 1 -attached halogens intercalated exactly between the -1 and +1 DNA bases, deeply toward the cleavage site and were stabilized by three H-bonds each and an array of hydrophobic interactions with both the enzyme and the DNA. The most potent inhibitory activities they showed in the test agree well with the proper docking results. Six compounds which did not intercalate and formed no H-bond showed no or very low inhibitory activities. Seven compounds that intercalated between the bases with one to four H-bonds but not deeply enough toward the cleavage site showed intermediate activities. The structure-activity relationship was consistent with the experimental data. The ternary complex presented potential binding mode of each compound and thus could provide a rational basis for novel inhibitor design to develop potent anticancer drugs targeting TOP1.

Correlation between the Binding Mode and Inhibitory Activity of Benz[f]indole-4,9-dione Analogs with Human Topoisomerase I-DNA