Benzofuran-2-Carboxamide Derivatives as Immunomodulatory Agents Blocking the CCL20-Induced Chemotaxis and Colon...

Area of Science:

• Medicinal Chemistry
• Immunology
• Oncology

Background:

• The CCL20/CCR6 signaling pathway is implicated in various autoimmune and non-autoimmune disorders.
• Targeting CCL20-mediated cell migration offers a therapeutic strategy for inflammatory bowel diseases and colorectal cancer.

Purpose of the Study:

• To investigate novel benzofuran derivatives as modulators of the CCL20/CCR6 axis.
• To identify compounds inhibiting CCL20-induced chemotaxis and colon cancer cell proliferation.

Main Methods:

• Exploration of the chemical space around the benzofuran scaffold of MR120.
• Functional screening of C4 and C5-substituted derivatives for inhibition of CCL20-induced chemotaxis in human peripheral blood mononuclear cells (PBMC).
• Assessment of cytotoxic, cytostatic, and antiproliferative activity of selected compounds against colon cancer cell lines.

Main Results:

• C4 and C5-substituted benzofuran derivatives were identified as potent inhibitors of CCL20-induced PBMC chemotaxis.
• Compounds 16e and 24b demonstrated significant inhibition of colon cancer cell line growth.
• The identified compounds exhibit cytotoxic/cytostatic and antiproliferative effects.

Conclusions:

• Novel benzofuran derivatives effectively modulate the CCL20/CCR6 axis.
• These compounds represent promising therapeutic agents for inflammatory diseases and colorectal cancer.