Bakuchiol and Related Compounds From <i>Psoralea glandulosa</i> as Potent Inhibitors of <i>Saprolegnia</i> sp.: A Combined In Vitro and In Silico Study

<jats:title>ABSTRACT</jats:title>
<jats:p>
<jats:italic>Saprolegnia</jats:italic>
sp., a water mold causing significant economic losses in aquaculture, necessitates sustainable alternatives to chemical treatments. This study investigated the resinous exudate of
<jats:styled-content style="fixed-case">
<jats:italic>Psoralea glandulosa</jats:italic>
</jats:styled-content>
and its derivatives as inhibitors of
<jats:styled-content style="fixed-case">
<jats:italic>Saprolegnia parasitica</jats:italic>
</jats:styled-content>
and
<jats:styled-content style="fixed-case">
<jats:italic>S. australis</jats:italic>
</jats:styled-content>
. Through in vitro assays and in silico molecular docking, the research aimed to determine the inhibitory efficacy and mechanism of action of these natural compounds. The results identified 3‐hydroxybakuchiol (2) as the most potent agent. It demonstrated superior minimum inhibitory concentration (MIC) values of 50 μg/mL against
<jats:styled-content style="fixed-case">
<jats:italic>S. parasitica</jats:italic>
</jats:styled-content>
and 25 μg/mL against
<jats:styled-content style="fixed-case">
<jats:italic>S. australis</jats:italic>
</jats:styled-content>
, surpassing the commercial control, bronopol. Its minimum oomyceticidal concentration (MOC) was also confirmed at low levels (50–75 μg/mL). Molecular docking analysis revealed that compound 2 has a high binding affinity for two crucial proteins in
<jats:italic>Saprolegnia</jats:italic>
: host‐targeting protein 1 (Htp‐1) and plasma membrane ATPase. These findings suggest that compound 2 acts as a potent dual inhibitor, with its free hydroxyl group being critical for its activity. This study positions 3‐hydroxybakuchiol as a promising lead compound for developing new, safer, natural‐based therapies to control saprolegniasis in the aquaculture industry.
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