New Nonsteroidal Molecules as Blockers of the Steroidogenic Pathway

    January 2022 in “ Current Enzyme Inhibition ”
    Jhoan Piermattey, Maicol Ahumedo, Yvonne Heuze, Juan Rodríguez Soriano, Marisa Cabeza
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    TLDR New nonsteroidal molecules can potentially increase dihydrotestosterone in neurons by blocking certain enzymes, without affecting prostate and seminal vesicle weight.
    The research examined the biological activity of new nonsteroidal derivatives of 2-aminonaphthalene-1,4-dione as inhibitors of the aldo-keto reductase 1 enzymes (AKR1C1, AKR1C2). The synthesized derivatives, 2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione, inhibited AKR1C1 and AKR1C2 enzyme activity with IC50 values of 420 nM and 1.95 μM, and 300 nM and 1.52 μM, respectively. They also prevented the formation of 3α and 3β-androstanediols but did not bind to androgen receptors or reduce prostate and seminal vesicle weight. The study concluded that these derivatives could potentially be used therapeutically via direct nasal administration in aged patients to increase dihydrotestosterone in neurons by inhibiting AKR1C1 and AKR1C2 enzyme activity, leading to the accumulation of dihydrotestosterone in androgen-dependent glands.
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