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Tyrosinase, a key enzyme in melanin synthesis, serves as a primary target for developing depigmenting agents. The search for novel tyrosinase inhibitors is needed due to the adverse effects of current inhibitors. This study evaluated 16 -thiourea derivatives using and methods, identifying compound , with chlorine substituents, as the most potent inhibitor. Compound outperformed kojic acid in inhibiting mushroom tyrosinase activity and interacted with catalytic copper ions and active site residues, as revealed by molecular docking and copper-chelating assay. Molecular dynamics simulation and MM/PBSA-based free energy calculations confirmed the greater stability and binding affinity of the compound -tyrosinase complex in an aqueous environment compared to kojic acid-tyrosinase complex. Melanin assay revealed that compound significantly suppressed melanin production in B16F10 melanoma cells, showing stronger anti-melanogenic activity than kojic acid. Drug-likeness predictions confirmed its compliance with Lipinski's rule of five, supporting -thiourea derivatives as promising tyrosinase inhibitors.

To identify novel tyrosinase inhibitors, a series of isocryptolepine ‘aza’ type acyl thiourea analogs (6a–6h) were designed and synthesized using a multistep strategy. Spectroscopic methods including FTIR, UV–vis, 1H NMR, 13C NMR, and EI-MS were utilized for detailed analysis of compounds. Their tyrosinase inhibitory activities were evaluated in vitro, demonstrating superior potency compared with kojic acid (IC50 = 16.83 ± 1.162 μM). The synthesized compounds exhibited IC50 values ranging from 0.832 ± 0.03 to 7.945 ± 0.63 μM, with compound 6g emerging as the most potent inhibitor (IC50 = 0.832 ± 0.03 μM). Kinetic studies revealed competitive inhibition by compound 6g, highlighting its potential as a lead candidate for treating tyrosinase-mediated hyperpigmentation. Additional evaluations showed that these compounds also effectively inhibited other enzymes involved in cancer progression, indicating their broad therapeutic potential. Molecular modeling studies against the tyrosinase enzyme (PDB: 4OUA) confirmed strong binding interactions, while structure-activity relationship analyses provided insights into their inhibitory mechanisms. Geometry optimization of the compounds, supporting their favorable molecular properties. Drug-likeness evaluations further validated the potential of these analogs as promising anti-tyrosinase agents. Overall, this study establishes compound 6g and its analogs as compelling candidates for further development in hyperpigmentation and cancer therapeutics.

Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction.

For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as organocatalysts, chelators, drug candidates, etc. The review focuses on the family of chiral thioureas, presenting an overview of the current state of knowledge on their synthesis and selected applications in stereoselective synthesis and drug development.

Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl–(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models.

Aliphatic amines strongly coordinate, and therefore easily inhibit, the activity of transition-metal catalysts, posing a marked challenge to nitrogen-hydrogen (N–H) insertion reactions. Here, we report highly enantioselective carbene insertion into N–H bonds of aliphatic amines using two catalysts in tandem: an achiral copper complex and chiral amino-thiourea. Coordination by a homoscorpionate ligand protects the copper center that activates the carbene precursor. The chiral amino-thiourea catalyst then promotes enantioselective proton transfer to generate the stereocenter of the insertion product. This reaction couples a wide variety of diazo esters and amines to produce chiral α-alkyl α–amino acid derivatives.

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

A series of six closely related acyl thiourea derivatives featuring adamantyl/noradamantyl groups at the 1‐acyl position and 3‐trihalophenyl substituents at the thiourea moiety are comprehensively characterized through spectroscopic, computational, and X‐ray crystallographic methods. Vibrational spectroscopy (IR and Raman) reveals significant redshifts in the NH and CO stretching bands, confirming the presence of strong intramolecular NH···OC hydrogen bonds. Conformational analysis using molecular mechanics and DFT calculations identifies several conformers, with the most stable adopting an S‐shaped geometry where the CO and CS bonds are oppositely oriented—a configuration that was experimentally validated by single‐crystal X‐ray diffraction. In the solid state, crystal packing is governed by hydrogen‐bonding interactions (H···OC and H···SC) facilitated by the acyl‐thiourea core. The bulky adamantyl/noradamantyl groups impose steric constraints, whereas the halogenated phenyl rings promote stabilizing π‐stacking and halogen interactions. Biological evaluation demonstrates limited antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Burkholderia cenocepacia, and Staphylococcus aureus, but moderate cytotoxicity against A549, 16HBE14o‐, and HaCaT cell lines (IC50 = 25–100 μM). A series of adamantyl‐based acyl thioureas with trihalophenyl groups is characterized using spectroscopic, computational, and crystallographic methods. Strong intramolecular hydrogen bonds and stable S‐shaped conformations are identified. Crystal packing is influenced by hydrogen bonding and π‐stacking interactions. While antimicrobial activity is limited, the compounds exhibit moderate cytotoxicity against lung and skin cell lines (IC50 = 25–100 μM).

This study reports a novel analytical approach for the simultaneous determination of ethylene-thiourea (ETU) and propylene-thiourea (PTU) in fruits and vegetables by (reverse phase) high-performance liquid chromatography (HPLC) coupled to inductively coupled plasma-tandem mass spectrometry (ICP-QQQMS or ICP-MS/MS). A baseline separation of ETU and PTU was achieved in less than 5 min. A robust method validation by using the accuracy profile approach was performed by carrying out four measurement series in duplicate at six different levels over a timespan of 4 weeks (different days). The recovery factors ranged from 87 to 101% for ETU and from 98 to 99% for PTU (depending on the spiking level). The coefficient of variation in terms of repeatability (CVr) ranged from 1 to 4.7% for ETU and from 1.8 to 3.9% for PTU (depending also on the analyte level) while the coefficient of variation in terms of intermediate reproducibility (CVR) ranged from 3.4 to 10% for ETU and from 1.8 to 10.8% for PTU. The limit of quantification was 0.022 mg kg−1 (wet weight) for ETU and 0.010 mg kg−1 (ww) for PTU. This novel approach was proved to be highly robust and suitable for the determination of ETU and PTU in foodstuffs of vegetal origin.

Nosocomial fungal infections caused by Candida auris pose a threat to public health due to their increased resistance to common antifungal drugs. Four thiourea derivatives of 2-thiophenecarboxylic acid were evaluated for their antifungal and antioxidant activity. The antifungal activity of the compounds was tested against strains of C. auris isolated from a hospital in Romania. With a notable inhibitory effect on C. auris biofilm growth and microbial adherence, the ortho-methylated derivative (SB2) showed the highest antifungal activity. Furthermore, emphasizing the impact of structural factors on the electron-donating capacity of these compounds, antioxidant activity assays (DPPH, FRAP, TEAC and CUPRAC) identified the SB2 compound as having the highest antihemolytic and antioxidant effects. The low cytotoxicity validated by hemocompatibility assays makes these compounds options for antifungal treatment. The results show that antifungal and antioxidant action is greatly influenced by structural modifications, especially the position of the methyl group on the aromatic ring. The possible clinical uses of these molecules as drugs for the treatment of multidrug-resistant C. auris infections needs further investigation.