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

August 2025 in “ ACS Omega ”

Kulpornsorn Isswanich, Pattara Poungcho, Koonchira Buaban, Hathaichanok Chuntakaruk, Kamonpan Sanachai, Chaisak Chansriniyom, Thanyada Rungrotmongkol, Wanchai De‐Eknamkul, Supakarn Chamni

bis(trifluoromethyl) phenyl hydroxycinnamate derivatives nonsteroidal inhibitors human steroid 5α-reductase type-1 SRD5A1 androgenetic alopecia AGA caffeic acid ferulic acid finasteride dutasteride dihydrotestosterone DHT hair follicles 5-alpha reductase Propecia Avodart

From the encyclopedia

Ferulic acid →

Finasteride →

Frontline, gold standard treatment for combatting androgenic alopecia

Dutasteride →

Heavy duty finasteride that comes with higher risks

Studysummary This study synthesized and evaluated hydroxycinnamate derivatives for their ability to inhibit human SRD5A1, finding that three compounds showed significant inhibitory activity and low cytotoxicity. Compound 10a notably reduced SRD5A1 protein expression in cells, suggesting potential for nonsteroidal treatment of androgen-related conditions. Our plain-language summary of this paper — not a Tressless recommendation.

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.

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