A set of novels 2-thiohydantoin derivatives were synthesized and enaminone function was discussed at position 5 using DMFDMA catalyst which result in formation of pyrazole, isoxazole, benzoxazepine by using reagents such as hydrazine, hydroxylamine and 2-aminothiophenol. These newly synthesized compounds were evaluated for their antioxidant and antiproliferative activity. In vitro studies on the effect of 2-thiohydantoin on scavenging 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) confirmed the free radical scavenging and antioxidant activity of 2-thiohydantoin. The synthesized compounds show significant antioxidant activity. The in vitro antitumor activity of 2-thiohydantoin on MCF7 (breast) and PC3 cells (prostate) was evaluated using MTT assay. Some of the synthesized compounds show significant to moderate antiproliferative properties compared to reference drug erlotinib. Among all, compound 4a exhibit potent antitumor properties against MCF7 and PC3 cancer cell lines with IC50 = 2.53 ± 0.09 /ml & with IC50 = 3.25 ± 0.12 µg/ml respectively and has potent antioxidant activity with IC50 = 10.04 ± 0.49 µg/ml.

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 μM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 μM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 μM and IC50 of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni.

Novel fungicidal agents were designed based on the combination of two privileged scaffolds, thiohydantoin and spirocyclic butenolide, which are widely found in natural products. The synthesized compounds were characterized by 1H NMR, 13C NMR, and high-resolution electrospray ionisation mass spectrometry. The in vitro antioomycete activity evaluation showed that most of the compounds exhibited excellent inhibitory activities against different developmental stages in the life cycle of pathogenic oomycete Phytophthora capsici. Compound 5j could inhibit the mycelial growth, sporangium production, zoospore release, and cystospore germination significantly with EC50 values of 0.38, 0.25, 0.11, and 0.026 μg/mL, respectively. The in vivo antifungal/antioomycete bioassay results revealed that the series of compounds generally showed outstanding control efficacies against the pathogenic oomycete Pseudoperonospora cubensis, and compounds 5j, 5l, 7j, 7k, and 7l possessed broad-spectrum antifungal activities against the test phytopathogens. The in vivo protective and curative efficacies against P. capsici of the representative compound 5j were excellent, which were better than those of azoxystrobin. More prominently, 5j significantly promoted the biomass accumulation of the root system and reinforced the cell wall by callose deposition. The pronounced upregulation of immune response-related genes indicated that the active oomycete inhibitor 5j also functioned as a plant elicitor. Transmission electron microscopy observation and the enzyme activity test demonstrated that the mechanism of action of 5j was to bind to the pivotal protein, complex III on the respiratory chain, which resulted in a shortage of energy supply. Molecular docking results exhibited that compound 5j appropriately matched with the Qo pocket and had no interaction with the most commonly mutated site Gly-142, which may be of significant benefit in Qo fungicide resistance management. Compound 5j showed great advantages and potential in oomycete control, resistance management, and induction of disease resistance. A further investigation of 5j with a unique structure might have direct implications for the creation of novel oomycete inhibitors against plant-pathogenic oomycetes.

Because androgen receptor (AR) signalling is important for the development and progression of prostate cancer (PC), AR antagonists are utilized in clinical practices to treat PC and are referred to as androgen deprivation therapy (ADT). However, continued administration of AR antagonists often results in the development of resistance, known as castration-resistant prostate cancer (CRPC). Despite castration, it has been demonstrated that AR signalling continues to be fundamental to tumour growth. In this regard, a series of readily synthesizable 4,4-dimethylimidazolidine-2-one pharmacophore-based AR antagonists (FAR01-FAR11) were designed and synthesized. Androgen-dependent LNCaP PC cell line was used to test the AR-antagonist activity of these compounds in vitro and compared with the U.S. Food and Drug Administration (FDA) approved second-generation enzalutamide. In our previous work, rigid thiohydantoin pharmacophore in enzalutamide is replaced by the flexible 4,4-dimethylimidazolidin-2-one. In order to improve the flexibility further, one methylene group is introduced between the pharmacophore and one of the aromatic ring. Despite the fact that the amide functional group is a crucial characteristic for building AR antagonists, this class of molecules lacks one. FAR06 has the exact same activity as enzalutamide (IC50 : 0.782 μM) with an IC50 value of 0.801 μM among the series of compounds.

This study assessed the effect of a primer containing 10-methacryloyloxydecyl-(2-thiohydantoin-4-yl)propionate (MDTHP) on the bonding of noble metal alloys to an acrylic resin. Three noble metal alloys were selected as adherends, and V-Primer containing 6-(4-vinylbenzyl-n-propyl)amino-1,3,5-triazine-2,4-dithione was used as a comparative control. The disk specimens of each noble metal alloy were wet-ground and divided into three conditions: specimens primed with MDTHP primer or V-Primer, and specimens without priming. An acrylic resin was bonded to each specimen, and the specimens were performed the shear bond test. The MDTHP primer showed higher shear bond strength than the V-Primer for all specimens. X-ray photoelectron spectroscopic analysis showed that MDTHP was adsorbed on the Au-Pt-Pd alloy surface even after acetone cleaning. MDTHP binds not only with Cu but also with Au and Ag, promoting the bond strength of noble metal alloys. The effectiveness of MDTHP on dental noble metal alloys was suggested.

The purpose of this study was to assess the effects of an experimental primer containing acetone solution and a sulfur-containing functional monomer, 10-methacryloyloxydecyl-(2-thiohydantoin-4-yl)propionate (MDTHP), on the bonds between noble metals and acrylic resin.
The experimental primer used as the control for comparison consisted of 6-(4-vinylbenzyl-n-propyl)amino-1,3,5-triazine-2,4-dithione (VBATDT) in acetone. These primers were prepared as equimolar functional monomers (0.1 mol%). A self-polymerizing acrylic resin initiated with tri-n-butylborane (TBB) was used as the luting agent. Four elemental metal disks (silver, copper, palladium, and gold) were used as adherend specimens. All the disks were wet-ground with silicon carbide paper (#1500). Bonding reactions were performed on 12 combinations of the four metals, and the disks were either primed with MDTHP or VBATDT or were unprimed (control). Shear bond strengths were determined pre- and post-thermocycling (5-55 °C, dwell time 60 s, 20,000 cycles). The results were statistically analyzed via a non-parametric test (α = 0.05).
The post-thermocycling shear bond strengths of the MDTHP primer were as follows (median, n = 11): 13.2 MPa on silver, 25.9 MPa on copper, 4.1 MPa on palladium, and 11.3 MPa on gold. The MDTHP primer showed higher post-thermocycling shear bond strength on all the four metals. Additionally, on silver and copper, the MDTHP bond strengths were higher than on the other metals.
Within the limitation of current of experimental setting, the MDTHP compound may be applicable as a functional monomer for bonding noble metal alloys.

On the basis of the scaffolds widely used in drug design, a series of novel spirooxindole derivatives containing hydantoin, thiohydantoin, urea, and thiourea moieties have been designed, synthesized, characterized, and first evaluated for their biological activities. The diastereoselectivity mechanism is proposed, and the systematic conformational analysis is performed. The bioassay results show that the target compounds possess moderate to good antiviral activities against tobacco mosaic virus (TMV), among which compound 22 shows the highest antiviral activity in vitro as well as inactivation, curative, and protection activities in vivo (45 ± 1, 47 ± 3, 50 ± 1, and 51 ± 1%, 500 mg/L, respectively), higher than ribavirin (38 ± 1, 36 ± 1, 38 ± 1, and 36 ± 1%, 500 mg/L, respectively). Thus, compound 22 is a promising candidate for anti-TMV development. Most of these compounds show broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi and selective fungicidal activities against Physalospora piricola, Sclerotinia sclerotiorum, and Rhizoctonia cerealis. Additionally, some of these compounds exhibit insecticidal activity against Culex pipiens pallens, Mythimna separata, Helicoverpa armigera, and Pyrausta nubilalis. Compound 17 exhibits the highest larvicidal activity (LC50 was 0.32 mg/L) against C. pipiens pallens.

Stable, nonracemic axially chiral hemiaminals (O,N-hemiacetals) have been synthesized stereoselectively from lithium aluminum hydride (LiAlH4 ) reductions of nonracemic 5-methyl- and 5-isopropyl-3-(o-aryl)-2-thioydantoins in tetrahydrofuran (THF) at room temperature in 10 min. Predominantly S-configured hemiaminals at C-4 of the heterocyclic ring were produced from the S-configured thiohydantoins at C-5 (by 80% when the C5 substituent is methyl and by 97% when it is isopropyl). The configuration at C-5 was retained during the reduction reaction. The stereochemical outcome of the axially chiral hemiaminals resulted from their conformational preferences.

Very recently, we have reported the synthesis and evaluation of biological properties of new merocyanine dyes composed of triphenylamine moiety, π-aromatic spacer, and rhodanine/2-thiohydantoin-based moiety. Interestingly, 2-thiohydantoin has never been studied before as an electron-accepting/anchoring group for the dye-sensitized solar cells (DSSCs). In the presented study, we examined the applicability of 2-thiohydantoin, an analog of rhodanine, in DSSC technology. The research included theoretical calculations, electrochemical measurements, optical characterization, and tests of the solar cells. As a result, we proved that 2-thiohydantoin might be considered as an acceptor/anchoring group since all the compounds examined in this study were active. The most efficient device showed power conversion efficiency of 2.59%, which is a promising value for molecules of such a simple structure. It was found that the cells\' performances were mainly attributed to the dye loading and the ICT molecular absorption coefficients, both affected by the differences in the chemical structure of the dyes. Moreover, the effect of the aromatic spacer size and the introduction of carboxymethyl co-anchoring group on photovoltaic properties was observed and discussed.

A new series of hybrid structures 14a-l containing thiohydantoin as anti-cancer moiety and pyrazole core possessing SO2Me pharmacophore as selective COX-2 moiety was designed and synthesized to be evaluated for both anti-inflammatory and anti-cancer activities. The synthesized compounds were evaluated for their COX inhibition, in vivo anti-inflammatory activity, ulcerogenic liability, in vitro cytotoxic activity and human topoisomerase-1 inhibition. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Also, all derivatives were significantly less ulcerogenic (ulcer indexes = 2.64-3.87) than ibuprofen (ulcer index = 20.25) and were of acceptable ulcerogenicity when compared with the non-ulcerogenic reference drug celecoxib (ulcer index = 2.99). Regarding anti-cancer activity, most of the target derivatives showed activities against A-549, MCF-7 and HCT-116 cell lines (IC50 = 5.32-17.90, 3.67-19.04 and 3.19-14.87 µM respectively) in comparison with doxorubicin (IC50 = 0.20, 0.50 and 2.44 µM respectively). Compound 14a inhibited the human topoisomerase-1 with IC50 = 29.7 µg/ml while 14b and 14c showed more potent inhibitory activity with IC50 = 26.5 and 23.3 µg/ml. respectively in comparison with camptothecin (IC50 = 20.2 µg/ml). Additionally, COX-2 and human topoisomerase-1 docking studies were carried out to explain the interaction of the synthesized hybrid structures 14a-l with the target enzymes.