<i>In silico</i> and <i>in vitro</i> Identification of Compounds with Dual Pharmacological Activity against Metionyl‐tRNA Synthetase and Isoleucyl‐tRNA Synthetase of <i>Staphylococcus aureus</i>

The spread of drug-resistant Staphylococcus aureus (S. aureus) in hospitals and communities poses a serious medical threat. This study aimed to identify aminoacyl-tRNA synthetase inhibitors with antimicrobial activity against S. aureus. In silico structure-based drug screening using docking molecular dynamics simulations (MDS) was performed targeting metionyl-tRNA (saMetRS). Ten candidate compounds were selected by compound 3D structure library 154,118 compounds. One (Compound 9) showed strong inhibitory effect growth inhibition studies epidermidis. From the experiments verifying dose-dependent effect, IC50 value Compound 9 determined be 3.74 μM. MDSs predicted that exhibits saMetRS isoleucyl-tRNA synthetase, which belongs same subclass Ia. its polypharmacological is not susceptible resistance expected have enhanced efficacy.