Background: Thiohydantoins are an important class of heterocyclic compounds in drug
discovery since they are related to a wide range of biological properties including antimicrobial activity.
Objective: The objective of this study was to synthesize a series of thiohydantoins derived from Laminoacids
and to evaluated their inhibitory effect on the growth of Gram-negative and Grampositive
Methods: All title compounds were synthetized by reaction of L-amino acids with thiourea or ammonium
thiocyanate. Their antimicrobial activities were evaluated against bacterial strains by broth
microdilution assays. The time-kill kinetics, the antibiofilm activity and the cytotoxicity to mammalian
cells were determined for the compound that exhibited the best antimicrobial profile (1b).
Results: Eleven thiohydantoins were readily obtained in good yields (52-95%). In general, thiohydantoins
were more effective against Gram-positive bacteria. Compound 1b (derived from Lalanine)
showed the best antibacterial activity against Staphylococcus epidermis ATCC 12228 and
S. aureus BEC 9393 with MIC values of 940 and 1921 µM, respectively. The time-kill kinetics
demonstrated time-dependent bactericidal effect in both strains for this derivative. Besides, 1b also
exhibited antibacterial activity against biofilms of S. epidermidis ATCC 12228, leading to a 40%
reduction in their metabolic activity compared to the untreated control. No cytotoxicity of 1b to
mammalian cells was observed at MIC values.
Conclusion: The data reported herein indicate relevant antimicrobial activity of thiohydantoins derived
from L-aminoacid, mainly 1b, as potential pharmacophore to guide further chemical modification
aiming at the search for new and improved antimicrobial agents.