Caffeic Acid N-[3,5-Bis(Trifluoromethyl)Phenyl] Amide as a Non-Steroidal Inhibitor for Steroid 5α-Reductase Type 1 Using a Human Keratinocyte Cell-Based Assay and Molecular Dynamics

    December 2022 in “ Scientific Reports
    Aye Chan Khine Lin, Ponsawan Netcharoensirisuk, Kamonpan Sanachai, Warongrit Sukma, Chaisak Chansriniyom, Chatchai Chaotham, Wanchai De-Eknamkul, Thanyada Rungrotmongkol, Supakarn Chamni
    TLDR Compound 4 is a promising treatment for hair loss with low toxicity.
    The study identifies caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide (compound 4) as a promising non-steroidal inhibitor of steroid 5α-reductase type 1 (SRD5A1), relevant for treating androgenic alopecia. Using human keratinocyte (HaCaT) cells, compound 4 showed significant inhibition of SRD5A1 with an IC50 of 1.44 ± 0.13 µM and low cytotoxicity. It was more potent than known inhibitors like avicequinone C, finasteride, and dutasteride. Molecular dynamics simulations and in vitro studies confirmed that compound 4 effectively suppressed SRD5A1 protein expression and reduced dihydrotestosterone (DHT) production, suggesting its potential as a therapeutic agent for androgenic alopecia.
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