In Vitro Antimicrobial Screening of Benzoylthioureas: Synthesis, Antibacterial Activity toward Streptococcus agalactiae and Molecular Docking Study

Abstract Herein, twenty‐six benzoylthioureas were evaluated for their antimicrobial activity against different bacterial and fungal species. Two 4‐substituted benzoylthiourea, one benzoylurea and one benzoylguanidine derivatives were further synthesized to identify the most promising compound. Eight compounds were active against at least one microbial species tested. N ‐(butylcarbamothioyl)‐benzamide ( 1 e ) exhibited the best antimicrobial activity towards Streptococcus agalactiae (group B Streptococcus ‐GBS), including clinical isolates susceptible or resistant to clindamycin and/or erythromycin and azithromycin. 1 e presented a bacteriostatic effect, causing morphological and ultrastructural alterations on planktonic cells, and decreased the metabolic activity of GBS biofilms. No hemolytic and cytotoxicity to mammalian cells were detected for 1 e , that also displayed drug‐likeness properties. Molecular docking was performed on Streptococcus pneumoniae enoyl‐ACP reductase obtained by homology modeling. 1 e showed relevant interactions with the GBS enoyl‐ACP reductase enzyme. N ‐(butylcarbamothioyl)‐benzamide may be a good starting point for the development of new antimicrobials against GBS.