Synthesis and Evaluation of Biological Activities of Aziridine Derivatives of Urea and Thiourea

Abstract

In the present paper, we report the synthesis and evaluation of in vitro antimicrobial activities of aziridine-thiourea derivatives. A series of aziridines in reaction with isocyanates and isothiocyanates to obtain urea and thiourea derivatives were used. The structures of all new products were confirmed based on spectroscopic data (1H-NMR, 13C-NMR, HR-MS). These compounds were screened for their in vitro antimicrobial activity against a panel of Gram-positive and Gram-negative strains of bacteria. Six of the tested compounds appeared to be promising agents against reference strains of Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis. Subsequently, compounds exhibiting promising antibacterial activity were tested against twelve clinical isolates of S. aureus from three different sources of infection. The most bactericidal compounds (MIC = 16–32 µg/mL) showed better antibacterial activity against MRSA than ampicillin and streptomycin. The in vitro cytotoxicity analysis on L929 murine fibroblast and HeLa human tumor cell line using the MTT assay allowed us to select the least toxic compounds for future investigation.

Thiosemicarbazide Derivatives Decrease the ATPase Activity of Staphylococcus aureus Topoisomerase IV, Inhibit Mycobacterial Growth, and Affect Replication in Mycobacterium smegmatis

“…Both compounds were tested previously against Gram-positive reference strains of S. aureus , S. epidermidis , Micrococcus luteus , and Bacillus cereus [ 37 , 38 ]. To expand the range of the analyzed strains, we decided to test a set of 12 clinical strains of S. aureus described in [ 51 ], including two MRSA strains (D15 and D17; Table 3 ), as well as two reference representatives of the Mycobacterium genus, namely M. smegmatis mc 2 155 and M. tuberculosis H37Rv ( Table 4 ).…”

“…The in vitro antimicrobial activity of compounds 4 and 7 was evaluated using twelve clinical isolates of S. aureus received from the collection of the Department of Immunology and Infectious Biology, University of Łódź (described in [ 51 ]). All strains were kept frozen at −80 °C in Tryptic soy broth with 15% glycerol until testing.…”

Synthesis of Imidazolidinone, Imidazolone, and Benzimidazolone Derivatives through Oxidation Using Copper and Air

“…Urea derivatives play an important role in medicinal chemistry, 1,2 as they show many biological and pharmacological activities, e.g. cofactor Biotin, 3 Kealiiquinone from Micronesian sponge, 4 antagonist Naamidine A, 5 and cytotoxin Agelastatin A (Figure 1).…”

Enantiodivergent Aldol Condensation in the Presence of Aziridine/Acid/Water Systems

“…Chiral catalysts 1-10 (Figure 2) were synthesized using a two-step synthesis from chiral, optically pure NH-aziridines [22] according to a procedure described earlier [23,24]. Two equivalents of enantiomerically pure chiral aziridines reacted with one equivalent of ZnBr 2 at 80 • C without solvent.…”

“…Based on our experience in the field of asymmetric synthesis using aziridine-containing ligands/organocatalysts [19][20][21][22] and achieving very promising preliminary results [23,24], we decided to synthesize a series of chiral, diastereomerically pure imines from 1-(2-aminoalkyl)aziridines and to investigate their catalytic activity in the enantiodivergent and/or diastereodivergent asymmetric aldol reaction in the presence of water. In 2019, Chen et al [25] prepared chiral aziridine imines and investigated its use in organocatalysis.…”