Design, Synthesis, and Biological Activity of TLR7-Based Compounds for Chemotherapy-Induced Alopecia

The study explored the design and synthesis of TLR7-based compounds to address chemotherapy-induced alopecia. Imiquimod was found to activate hair follicle stem cells, prompting premature hair cycle entry. A new compound, 6b, derived from quinoline, showed promising proliferation activity both in vitro and in vivo. Despite the aim to develop TLR7 agonists, biological assays revealed that five selected compounds acted as TLR7 antagonists. Molecular docking studies highlighted that these antagonists bind TLR7 differently, complicating dimer formation. The research provided insights into the potential therapeutic applications of TLR7 modulation in managing chemotherapy-induced hair loss.