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An in vitro inhibitory activity evaluation of caffeic acid (<jats:bold>1<\/jats:bold>) and its amide derivatives (<jats:bold>2<\/jats:bold>\u2009\u2212\u2009<jats:bold>4<\/jats:bold>) against the steroid 5\u03b1-reductase type 1 (SRD5A1) produced by human keratinocyte cells coupled with the non-radioactive high-performance thin-layer chromatography detection revealed that caffeic acid <jats:italic>N<\/jats:italic>-[3,5-bis(trifluoromethyl)phenyl] amide (<jats:bold>4<\/jats:bold>) was a promising non-steroidal suppressor, with a half-maximal inhibitory concentration (IC<jats:sub>50<\/jats:sub>) of 1.44\u2009\u00b1\u20090.13\u00a0\u00b5M and relatively low cytotoxicity with an IC<jats:sub>50<\/jats:sub> of 29.99\u2009\u00b1\u20098.69\u00a0\u00b5M. The regulatory role of compound <jats:bold>4<\/jats:bold> against SRD5A1 involved both suppression of SRD5A1 expression and mixed mode SRD5A1 inhibition. The K<jats:sub>i<\/jats:sub> value of compound <jats:bold>4<\/jats:bold> was 2.382\u00a0\u00b5M based on the whole-cell kinetic studies under specific conditions. Molecular docking and molecular dynamics simulations with AlphaFold generated the human SRD5A1 structure and confirmed the stability of compound <jats:bold>4<\/jats:bold> at the SRD5A1 catalytic site with greater interactions, including hydrogen bonding of the key M119 amino-acid residue than those of finasteride and dutasteride. 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