Explore the vast range of titles available.

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.

Novel three biologically active itaconimido thiourea derivatives (DI, DII and DIII) were synthesized via reaction of N -[4-(isothiocyanatecarbonyl)phenyl] itaconimide with either aniline, p-toluidine or p- amino benzoic acid, respectively. The radical polymerization of DI, DII and DIII in dimethyl sulfoxide using azobisisobutyronitrile initiator was successfully performed to produce three polymers that were denoted as PI, PII and PIII, respectively. Their chemical structures were confirmed by elemental analyses, FTIR, 1 H-NMR and mass spectra. They showed a high potency for growth inhibition of E. faecalis , S. epidermidis, E. coli, A. niger , C. neoformans and C. tropicalis . This is not only illustrated by their high inhibition zone diameters but also by their low minimum inhibitory concentrations. Some of them showed activities better than the reference drug Amphotericin B against all the tested fungi. DIII and PIII were safe on normal fibroblast cells of the lungs of the human (MRC-5 cells) through their evaluation using cytotoxic activity measurement. The thermal stability of PVC in the presence of DI–DIII and their polymers PI–PIII was evaluated. In comparison with DBLC, Cd–Ba–Zn stearate and n-OTM as reference stabilizers, DI–DIII and PI–PIII greatly stabilize PVC against thermal degradation. This is evidenced by increased initial decomposition temperatures and decreased weight losses at particular temperatures. It was found that the substituent group having an electron releasing nature that incorporated into DII and PII enhances their performance for PVC stabilization. DI–DIII and PI–PIII achieve a lower degree of discoloration and molecular weight alteration of PVC than the industrial stabilizers.

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.

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.

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).

Tyrosinase, a key enzyme in melanin synthesis, represents a crucial therapeutic target for hyperpigmentation disorders due to excessive melanin production. This study aimed to design and evaluate a series of indole–thiourea derivatives by conjugating thiosemicarbazones with strong tyrosinase inhibitory activity to indole. Among these derivatives, compound 4b demonstrated tyrosinase inhibitory activity with an IC50 of 5.9 ± 2.47 μM, outperforming kojic acid (IC50 = 16.4 ± 3.53 μM). Kinetic studies using Lineweaver–Burk plots confirmed competitive inhibition by compound 4b. Its favorable ADMET and drug-likeness properties make compound 4b a promising therapeutic candidate with a reduced risk of toxicity. Molecular docking revealed that the compounds bind strongly to mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (TYRP1), with compound 4b showing superior binding energies of −7.0 kcal/mol (mTYR) and −6.5 kcal/mol (TYRP1), surpassing both kojic acid and tropolone. Molecular dynamics simulations demonstrated the stability of the mTYR−4b complex with low RMSD and RMSF and consistent Rg and SASA values. Persistent strong hydrogen bonds with mTYR, along with favorable Gibbs free energy and MM/PBSA calculations (−19.37 kcal/mol), further support stable protein–ligand interactions. Overall, compound 4b demonstrated strong tyrosinase inhibition and favorable pharmacokinetics, highlighting its potential for treating pigmentary disorders.

Spectroscopic analysis of 1-(2-fluorophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea (FPTT) is reported. Experimental and theoretical analyses of FPTT, with molecular dynamics (MD) simulations, are reported for finding different parameters like identification of suitable excipients, interactions with water, and sensitivity towards autoxidation. Molecular dynamics and docking show that FPTT can act as a potential inhibitor for new drug. Additionally, local reactivity, interactivity with water, and compatibility of FPTT molecule with frequently used excipients have been studied by combined application of density functional theory (DFT) and MD simulations. Analysis of local reactivity has been performed based on selected fundamental quantum-molecular descriptors, while interactivity with water was studied by calculations of radial distribution functions (RDFs). Compatibility with excipients has been assessed through calculations of solubility parameters, applying MD simulations. Graphical abstract Reactive sites identified

Novel oral anticoagulants are frequently used for the pharmacotherapy of thromboembolic disorders but still have drawbacks and side effects. While numerous synthetic and semisynthetic derivatives of nontoxic isosteviol possess potential therapeutic properties, including anticoagulant activity. Besides, thiourea is recognized in medicinal chemistry research as a component of a common framework of many drugs or bioactive compounds. The present work combines molecular modeling and docking approach for searching and designing novel thiourea isosteviol-based compounds as potential FXa inhibitors. Elaborated regression model well reflects the relationships between experimentally determined anticoagulant activity and molecular descriptors and may be used for the prediction of FXa inhibitory activity of novel thiourea isosteviol compounds. Among 20 descriptors incorporated into the ANN model, 60% are 2D topological descriptors, 25% describe three-dimensional molecular structure, and remaining 15% belong to constitutional descriptors. Additionally, docking simulation confirms the prominent binding of the newly in silico designed molecules with the active sites of the protein, which may be the lead molecules and can be further optimized for the efficient pharmacodynamic and pharmacokinetic profiles. Based on the results obtained, thiourea derivatives of isosteviol with 3-chloro-4-fluorophenyl, 3-fluoro-4-chlorophenyl or 4-(oxazol-5-yl)phenyl substituent may be promising FXa inhibitors. Findings reported in the present work can be used as valuable information for the development of anticoagulants.

The continuously increasing global impact of fungal infections is requiring the rapid development of novel antifungal agents. Due to their multiple pharmacological activities, thiourea derivatives represent privileged candidates for shaping new drugs. We report here the preparation, physico-chemical characterization and bioevaluation of hybrid nanosystems based on new 2-((4-chlorophenoxy)methyl)-N-(substituted phenylcarbamo-thioyl)benzamides and Fe3O4@C18 core@shell nanoparticles. The new benzamides were prepared by an efficient method, then their structure was confirmed by spectral studies and elemental analysis and they were further loaded on Fe3O4@C18 nanostructures. Both the obtained benzamides and the resulting hybrid nanosystems were tested for their efficiency against planktonic and adherent fungal cells, as well as for their in vitro biocompatibility, using mesenchymal cells. The antibiofilm activity of the obtained benzamides was dependent on the position and nature of substituents, demonstrating that structure modulation could be a very useful approach to enhance their antimicrobial properties. The hybrid nanosystems have shown an increased efficiency in preventing the development of Candida albicans (C. albicans) biofilms and moreover, they exhibited a good biocompatibility, suggesting that Fe3O4@C18core@shell nanoparticles could represent promising nanocarriers for antifungal substances, paving the way to the development of novel effective strategies with prophylactic and therapeutic value for fighting biofilm associated C. albicans infections.

Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1H-NMR, 13C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.