Effect of hybrid compounds of stilbene and pentadienone on inhibition of tubulin polymerization

by Selleckchem | Mar 09 2023

Introduction: Tubulin polymerization inhibitors induce cancer cell death; therefore, they can be developed as chemotherapeutic agents. We hypothesized that hybrid compounds, including the trans-stilbene moiety contained in resveratrol and penta-1,4-dien-3-one contained in curcumin, could inhibit tubulin polymerization.

Methods: Twenty-six hybrid stilbene and pentadienone compounds were designed and synthesized. The cytotoxicity of the hybrid compounds against MDA-MB-231 human breast cancer cells was determined using a clonogenic long-term survival assay. The relationship between cytotoxicity and structural properties was evaluated. Biological activities, including inhibition of tubulin polymerization and cell cycle progression, were investigated to select compounds with excellent anticancer properties. The molecular binding mode between the selected compound and the α,β-tubulin dimers was investigated.

Results: Twenty-six hybrid stilbene and pentadienone compounds were designed and synthesized. Among them, compound 13 exhibited the highest inhibitory effect on the clonogenicity of MDA-MB-231 cells. Compound 13 induced the destabilization of tubulins and inhibited cell cycle progression at the G2/M phase. Through in silico molecular docking analysis, compound 13 was predicted to bind to the colchicine binding site of α, β-tubulin.

Conclusion: The stilbene and pentadienone hybrid compound 13 has a binding mode similar to that of colchicine. Compound 13 inhibited the clonogenicity of MDA-MB-231 cells through a mechanism that destabilizes tubulin polymerization, leading to cell cycle arrest at the G2/M phase.

Comments：

This study aimed to design and synthesize hybrid compounds that could inhibit tubulin polymerization and induce cancer cell death. The researchers designed 26 hybrid stilbene and pentadienone compounds and evaluated their cytotoxicity against MDA-MB-231 human breast cancer cells using a clonogenic long-term survival assay. They also investigated the relationship between cytotoxicity and structural properties and assessed the compounds' ability to inhibit tubulin polymerization and cell cycle progression.

Among the 26 compounds tested, compound 13 exhibited the highest inhibitory effect on the clonogenicity of MDA-MB-231 cells. This compound was found to destabilize tubulins and inhibit cell cycle progression at the G2/M phase. In silico molecular docking analysis predicted that compound 13 binds to the colchicine binding site of α,β-tubulin.

The study's results suggest that compound 13 has excellent anticancer properties and inhibits the clonogenicity of MDA-MB-231 cells through a mechanism that destabilizes tubulin polymerization, leading to cell cycle arrest at the G2/M phase. The researchers' findings suggest that stilbene and pentadienone hybrid compounds could be developed as chemotherapeutic agents for the treatment of cancer.