Synthesis of New Chromene Derivatives Targeting Triple-Negative Breast Cancer Cells

Area of Science:

• Oncology
• Medicinal Chemistry
• Cell Biology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and frequent drug resistance.
• Existing therapies, including taxane mitotic inhibitors, are often ineffective against TNBC.
• Novel therapeutic agents are urgently needed to combat TNBC progression and mortality.

Purpose of the Study:

• To synthesize and evaluate the efficacy of two novel chromene derivatives, C1 and C2, against TNBC.
• To investigate the mechanisms of action of C1 and C2 in TNBC cells.
• To assess the potential of C1 and C2 as chemotherapeutic agents for TNBC.

Main Methods:

• Synthesis of novel chromene derivatives C1 and C2.
• In vitro testing of C1 and C2 against luminal A and TNBC cell lines.
• Analysis of cellular effects including cell viability, mitotic arrest, apoptosis, and cytoskeleton disruption.
• In vitro assessment of cell migration and angiogenesis.
• In silico molecular docking to identify binding targets.

Main Results:

• C1 and C2 specifically inhibited TNBC cell viability without affecting luminal A cells.
• Compounds induced mitotic arrest, multinucleation, senescence, and apoptosis via the extrinsic pathway.
• Mechanisms involved inhibition of microtubule polymerization and F-actin cytoskeleton disruption.
• C1 and C2 attenuated TNBC cell migration and inhibited angiogenesis in vitro.
• In silico analysis indicated binding to the colchicine binding site of β-tubulin.

Conclusions:

• Novel chromene derivatives C1 and C2 demonstrate significant and specific anti-TNBC activity.
• These compounds exhibit potent anti-migratory and anti-angiogenic effects.
• The findings highlight the therapeutic potential of C1 and C2 as novel chemotherapeutic agents for triple-negative breast cancer.