Synthesis and Antimicrobial Activity of Thiohydantoins Obtained from L-Amino Acids

Abstract

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 bacteria. 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.

Thiohydantoins as Potential Antioxidant Agents: In vitro and in silico evaluation

“…Thiohydantoins ( 1 a – l ) were synthesized as previously described by de Carvalho et al., 2020 [20] . The in vitro antioxidant activity of thiohydantoins ( 1 a – l ) were determined by DPPH scavenging assays (Table 1).…”

Preliminary Studies of Antimicrobial Activity of New Synthesized Hybrids of 2-Thiohydantoin and 2-Quinolone Derivatives Activated with Blue Light

“…Other 2-thiohydantoin and rhodanine derivatives investigated by Tejchman et al [ 2 ] demonstrated no activity against Gram-negative bacteria, but some of them were active against Gram-positive ones. Thiohydantoins reported by Camargo de Carvalho et al [ 3 ] were more effective against Gram-positive bacteria, as well. The possible antibacterial mechanism of the hybrids of 2-thiohydantoin and rhodanine derivates reported by Tejchman et al [ 2 ] suggests “their interaction with molecular targets located on the surface of the cell membrane”.…”

“…Among already applied drugs, quinolones and thiohydantoin derivatives are used as chemotherapeutics and antibiotics. Compounds containing 2-thiohydantoin core reveal antibacterial [ 1 , 2 , 3 ], antifungal [ 4 ], antitumor [ 5 ], antiparasitic [ 6 ], and antiviral activity [ 7 ]. Compounds with 2-quinolone core are also known for their broad range of biological effects [ 8 , 9 ].…”

Effect of New 2-Thioxoimidazolidin-4-one Compounds against Staphylococcus aureus Clinical Strains and Immunological Markers’ Combinations

“…Moreover, the results illustrated a significant difference ( P < 0.05s) between the inhibition rate of treated biofilms and untreated biofilms. Consequently, the potential of exhibiting antibiofilm activity against biofilms of S. aureus is more by these compounds compared to the previous reports (it inhibited 40% S. epidermidis ATCC 12228 biofilm) [ 82 ]. So far, only a few studies have been found about inhibited biofilms by hydantoin compounds.…”

“…Generally, the compounds showed potentiating properties at concentrations from 31 to 125 µg/mL. us, these compounds have more potential than previously reported anti-S.aureus activity MIC values [80][81][82]; in addition to the tested bacteria, there are other virulent strains. Hydantoin derivatives are small molecules that have moderate antimicrobial activity which may be essential for reducing antibiotic resistance in the long run, besides being potent and having rapid antimicrobial activity against pathogenic bacterial strains [83].…”