The study identified 3-deoxy-7-phosphoheptulonate synthase (DAHP synthase), encoded by the aroG gene, as a promising bacterial protein from Gardnerella vaginalis for further analysis. DAHP synthase plays a crucial role in the shikimate pathway, which is responsible for producing essential aromatic amino acids such as tyrosine and tryptophan, as well as other related compounds.
As reported by azolifesciences.com, structurally, DAHP synthase exhibited stability, with hydrophobic regions organized in a globular formation. Its size made it an ideal candidate for drug targeting. Additionally, several DAHP synthase inhibitors were identified from the ZINC database, displaying properties such as high solubility, good oral bioavailability, and favorable pharmacokinetics. The safety evaluation suggested a low risk of hepatotoxicity, mutagenicity, and skin sensitivity, though conditions like pregnancy, renal impairment, liver cirrhosis, and steatosis could affect the absorption of these compounds.
Physiologically-based pharmacokinetic modeling, which analyzes absorption, distribution, metabolism, and excretion (ADME), revealed that the compound ZINC98088375 had the most effective systemic circulation and bioavailability. The research utilized a computational framework to pinpoint proteins in G. vaginalis as viable drug targets for the treatment of bacterial vaginosis.
DAHP synthase was identified as a key target due to its role in the bacterium’s amino acid pathways, and various inhibitors from the ZINC database were found to have suitable pharmacokinetic profiles. ZINC98088375 emerged as the most promising compound in terms of bioavailability and systemic circulation. Further in vitro and in vivo studies are needed to validate the efficacy of these potential therapeutic agents for clinical application.