The stilbene and dibenzo[b,f]oxepine derivatives as anticancer compounds

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Drug Discovery

Background:

• Cancer remains a leading cause of mortality worldwide, necessitating the development of novel therapeutic agents.
• Stilbene and oxepine derivatives are classes of compounds with known biological activities.
• Targeting tubulin, a key protein in cell division, is a validated strategy in cancer chemotherapy.

Purpose of the Study:

• To synthesize and evaluate the cytotoxic effects of novel stilbene and oxepine derivatives.
• To investigate the mechanism of action of the most active compounds, specifically their interaction with tubulin.
• To assess the selectivity of these compounds against cancer cell lines versus normal cell lines.

Main Methods:

• Synthesis of six stilbene and three oxepine derivatives.
• Cytotoxic assays using human cancer cell lines (HeLa, U87) and normal cell lines (EUFA30, HEK293).
• Flow cytometry analysis to assess cell death.
• Computer molecular modeling, including molecular docking studies on the colchicine-binding site of tubulin.

Main Results:

• Compounds 9-nitrobenzo[b]naphtho[1,2-f]oxepine (4), (E)-3,3',4,4',5,5'-hexamethoxystilbene (6), and 4-hydroxy-2',4'-dinitrostilbene (8) exhibited significant cytotoxic activity.
• Molecular docking confirmed the interaction of compounds 4, 6, and 8 with the tubulin protein.
• Compound 4 showed stronger tubulin binding than colchicine but lacked selectivity. Compounds 6 and 8 bound weaker than colchicine but demonstrated selectivity towards cancer cells.
• The most potent anti-cancer compounds demonstrated their activity through tubulin binding.

Conclusions:

• Compounds 6 and 8 represent promising lead compounds for developing selective anti-cancer drugs targeting tubulin.
• Further optimization of these compounds may lead to novel chemotherapeutic agents with improved efficacy and reduced side effects.
• The study validates tubulin as a viable target for the identified stilbene and oxepine derivatives in cancer treatment.