biostudies-literatureGalano-Frutos JJGobierno de AragonJPIAMRMinisterio de Ciencia e InnovaciónMICINNe27982https://www.ebi.ac.uk/biostudies/studies/S-EPMC11059415biostudies-literatureUnknown10(7)<h4>Objectives</h4>The rise of antibiotic-resistant <i>Streptococcus pneumoniae</i> (<i>Sp</i>) poses a significant global health threat, urging the quest for novel antimicrobial solutions. We have discovered that the human hormone l-thyroxine has antibacterial properties. In order to explore its drugability we perform here the characterization of a series of l-thyroxine analogues and describe the structural determinants influencing their antibacterial efficacy.<h4>Method</h4>We performed a high-throughput screening of a library of compounds approved for use in humans, complemented with ITC assays on purified <i>Sp</i>-flavodoxin, to pinpoint molecules binding to this protein. Antimicrobial <i>in vitro</i> susceptibility assays of the hit compound (l-thyroxine) as well as of 13 l-thyroxineHeliyonL-Thyroxine and L-thyroxine-based antimicrobials against Streptococcus pneumoniae and other Gram-positive bacteria.PMC11059415PID2022-141068NB-I00PID2019-107293 GB-I00E45_23RSchaible UEIguarbe VMamat UAinsa JASancho JMaity RGalano-Frutos JJVelazquez-Campoy AfalseL-Thyroxine and L-thyroxine-based antimicrobials against Streptococcus pneumoniae and other Gram-positive bacteria.<h4>Objectives</h4>The rise of antibiotic-resistant <i>Streptococcus pneumoniae</i> (<i>Sp</i>) poses a significant global health threat, urging the quest for novel antimicrobial solutions. We have discovered that the human hormone l-thyroxine has antibacterial properties. In order to explore its drugability we perform here the characterization of a series of l-thyroxine analogues and describe the structural determinants influencing their antibacterial efficacy.<h4>Method</h4>We performed a high-throughput screening of a library of compounds approved for use in humans, complemented with ITC assays on purified <i>Sp</i>-flavodoxin, to pinpoint molecules binding to this protein. Antimicrobial <i>in vitro</i> susceptibility assays of the hit compound (l-thyroxine) as well as of 13 l-thyroxine2024-01-01T00:00:00Z2024 Apr2026-06-01T11:31:27.607Z2026-04-08T11:52:48.237ZS-EPMC110594153868997310.1016/j.heliyon.2024.e27982