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

ABSTRACT: The development of steroid 5α-reductase inhibitors for the treatment of androgenetic alopecia remains challenging, primarily due to the unavailability of a crystal structure for human steroid 5α-reductase type-1 (SRD5A1) and the adverse effects associated with existing steroidal therapeutic agents such as finasteride and dutasteride. In this study, hydroxycinnamate derivatives were synthesized and evaluated for their inhibitory activity against SRD5A1 using an immortalized human keratinocyte cell-based assay coupled with nonradioactive high-performance thin-layer chromatography analysis. Three ferulate derivatives featuring 2',5'-, 3',4'-, and 3',5'-bis-(trifluoromethyl)-phenyl substituents (10a, 10b, and 10c) demonstrated inhibitory activity with half-maximal inhibito

SUBMITTER: Isswanich K 

PROVIDER: S-EPMC12391935 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature