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

A novel class of noscapine derivatives known as 9-arylimino noscapinoids was designed by substituting arylimino groups (Schiff bases) at the C-9 position. These molecules were docked with αβ-tubulin complex and a panel of three top scoring molecules, 4-6 based on docking score were screened out. These molecules bind tubulin with robust predicted binding energy of -37.24 kcal/mol and -45.41 kcal/mol for 4, -39.73 kcal/mol and -47.74 kcal/mol for 5, and -43.62 kcal/mol and -49.72 kcal/mol for 6 respectively compared to noscapine (-34.47 kcal/mol and -40.27 kcal/mol) using molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics/generalized Born surface area (MM/GBSA). These three molecules were chemically synthesized and demonstrated experimentally to bind tubulin with high affinity compared to noscapine. The anti-proliferative activity of 4-6 revealed inhibitory concentration (IC 50  value) in between 3.6 to 32.6 µM using MCF-7 and MDA-MB-231 human breast cancer cell lines and a group of primary breast tumor cells. All three molecules were shown to inhibit the mitotic progression at the G2/M phase and induce apoptosis to cancer cells at a different level. Thus, we conclude that 9-arylimino noscapinoids 4-6 have tremendous potential as chemotherapeutic agents for the treatment of breast cancer.

Structure Based Design of Tubulin Binding 9-Arylimino Noscapinoids: Chemical Synthesis and Experimental Validation Against Breast Cancer Cell Lines