Microwave-Enhanced Synthesis of 2-Styrylquinoline-4-Carboxamides With Promising Anti-Lymphoma Activity.

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Biology

Background:

• Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and common non-Hodgkin lymphoma.
• Novel therapeutic strategies are needed to address DLBCL heterogeneity and resistance.

Purpose of the Study:

• To design and synthesize a new series of 2-styrylquinoline-4-carboxamides.
• To evaluate the antiproliferative activity of these compounds against DLBCL cell lines.
• To investigate the mechanism of action of the most potent compounds.

Main Methods:

• Microwave-assisted organic synthesis (MAOS) was employed for efficient compound preparation.
• In vitro antiproliferative assays were conducted on various lymphoma cell lines.
• Cell cycle analysis, apoptosis assays, and reactive oxygen species (ROS) measurements were performed.

Main Results:

• 34 derivatives were synthesized, with 24 exhibiting in vitro antiproliferative activity.
• Compound 4i showed sub-micromolar IC50 values against DLBCL cell lines (e.g., SU-DHL-8, TOLEDO).
• Compound 4i induced G2/M cell cycle arrest, suppressed DNA synthesis, depolarized mitochondria, and increased ROS, activating apoptosis. It was non-toxic to PBMCs.

Conclusions:

• The quinoline scaffold is a promising chemotype for DLBCL drug discovery.
• MAOS is an effective method for synthesizing bioactive heterocyclic compounds.
• Compound 4i warrants further investigation as a potential DLBCL therapeutic agent.