Natural Product-Inspired Bis(Trifluoromethyl) Phenyl Hydroxycinnamate Derivatives as Promising Nonsteroidal Inhibitors of Human Steroid 5α-Reductase Type-1: Synthesis, In Vitro, and In Silico Studies

The study investigates bis(trifluoromethyl) phenyl hydroxycinnamate derivatives as nonsteroidal inhibitors of human steroid 5α-reductase type-1 (SRD5A1), an enzyme linked to androgenetic alopecia (AGA). These compounds, synthesized from caffeic and ferulic acids, were tested using in vitro assays and in silico studies, showing promise as alternatives to steroidal inhibitors like finasteride and dutasteride. The derivatives, particularly compound 10a, demonstrated effective SRD5A1 inhibition and maintained high cell viability, suggesting potential as topical treatments for AGA. The study emphasizes the potential of these nonsteroidal inhibitors in treating hair loss by targeting SRD5A1, which is predominantly expressed in hair follicles and contributes to excessive dihydrotestosterone (DHT) production.