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Phenylthiourea was synthesized for the first time with a yield of 75–80% based on thiourea, in the presence of various catalysts, and optimal conditions were identified for some reactions. At the same time, the condensation of their methylene-active molecules and various aldehydes in acidic media caused the synthesis of di-, tetra-, hexahydropyrimidinethiones, which are not known in the literature so far; the role of different catalysts in this process were comparatively studied. Synthesis of heterocyclic compounds containing phenol hydroxyl, mono-, dual-, triple-amine, -thion, and hydroxyl groups in the presence of ionic liquids, CCl3COOH CF3COOH, NiCl2.6H2O catalysts as well as in the increase of yield percentages showed that the use of environmentally and economically efficient ionic liquids among these catalysts allows to obtain purposeful compounds with the highest yield (95%). The inhibition of α-glycosidase, aldose reductase, and α-amylase enzymes by functionally substituted derivatives of thiourea and phenylthiourea (1a–1f) is then observed. Compound 1d displayed the lowest inhibitory effect against AR in these series with an IC50 value of 3.25 µM, whereas compound 1c compound displayed the highest inhibitory effect with an IC50 value of 1.46 µM. The enzymes α-amylase and α-glycosidase were also easily inhibited by these substances. All substances were examined for their capacity to inhibit the α-glycosidase enzyme, with Ki values ranging between 14.321.53 and 29.322.50 µM and IC50 values between 12.23 and 25.22 µM. Additionally, the IC50 values for the effective inhibition profile of the α-amylase, which was determined vary from 1.02 to 7.87 µM. [ABSTRACT FROM AUTHOR]

Cancer is a disease characterized by cells forming abnormally so that a buildup can cause lumps. Drug compounds used for anticancer treatment by chemotherapy become a severe problem because they have dangerous side effects and can affect patient’s quality of life. This study aims to discover new drug compounds with lowered toxicity effects. This was achieved by modifying their structures through synthesis, characterization, and estimating the interactions of the synthesized compounds with specific target receptors, utilizing a docking method. The result obtained was a synthesis yield of 36.2%. The characterization of complex compounds was characterized by the presence of a maximum wavelength of 273 nm and a molecular weight of 652 g/mmol, indicating the absorption of Co-O and Co-S at respective wavenumbers of 498 cm-1 and 604 cm- 1. The docking results showed that the Bis-(1-(3-Chlorobenzoyl)-3-Phenylthiourea) Cobalt (III) complex had the best activity on human estrogen receptor alpha (hER alpha) with a binding affinity value of - 9.40 kcal/mol and an inhibition constant of 0.129 M, which was lower than the comparison compound (cisplatin) and had a better pharmacokinetic profile than cisplatin. This study shows that the Bis-(1-(3-Chlorobenzoyl)-3-Phenylthiourea) Cobalt (III) complex is predicted to have potential as an anticancer candidate.

The primary challenge in chemotherapy for breast cancer stems from the limited effectiveness of existing drugs due to the diverse mutations, each requiring specific treatment. Consequently, it is essential to focus on the development of drugs specifically designed for anti-breast cancer therapy. In this investigation, we synthesized and evaluated compounds with methyl and nitro substituents on the para position in N-benzoyl-N'-phenylthiourea to examine their efficacy against breast cancer cells (MCF-7). Computational analyses demonstrated favorable interactions with EGFR, and experimental tests revealed IC50 values of 0.42 mM for the first compound and 0.07 mM for the second compound. Remarkably, the second molecule showed enhanced selectivity and cytotoxicity (SI value of 937.57) in comparison to the first compound, suggesting that it could be a promising drug for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Oxidative metabolism of rhododendrol (RD), a skin-whitening ingredient, by tyrosinase has caused leukoderma in a certain population of Japanese consumers. Toxic RD metabolites and reactive oxygen species are proposed causes for the melanocyte death. However, the mechanism by which reactive oxygen species are produced during RD metabolism remains elusive. Some phenolic compounds are known to act as suicide substrates for tyrosinase, resulting in release of a copper atom and hydrogen peroxide during its inactivation. We hypothesized that RD may be a suicide substrate for tyrosinase and that the released copper atom may be responsible for the melanocyte death through hydroxyl radical production. In line with this hypothesis, human melanocytes incubated with RD showed an irreversible decrease in tyrosinase activity and underwent cell death. A copper chelator, d -penicillamine, markedly suppressed the RD-dependent cell death without significantly affecting the tyrosinase activity. Peroxide levels in RD-treated cells were not affected by d -penicillamine. Given the unique enzymatic properties of tyrosinase, we conclude that RD acted as a suicide substrate and resulted in release of a copper atom and hydrogen peroxide, which would collectively impair melanocyte viability. These observations further imply that copper chelation may alleviate chemical leukoderma caused by other compounds. [Display omitted] • Rhododendrol (RD) inactivates tyrosinase in human primary melanocytes. • Copper chelation effectively alleviates RD-triggered melanocyte death. • Suicide substrate nature of RD is responsible for melanocyte death and leukoderma. [ABSTRACT FROM AUTHOR]

Abstract Background The bitter taste receptor gene TAS2R38 is a member of the human TAS2R gene family. Polymorphisms in TAS2R38 affect the ability to taste the bitterness of phenylthiourea (PTC) compounds, thus affecting an individual’s food preference and health status. Methods We investigated polymorphisms in the TAS2R38 gene and the sensitivity to PTC bitterness among healthy Chinese college students in Hubei province. The association of TAS2R38 polymorphisms and PTC sensitivity with body mass index (BMI), food preference, and health status was also analyzed. A total of 320 healthy college students were enrolled (male: 133, female: 187; aged 18–23 years). The threshold value method was used to measure the perception of PTC bitterness, and a questionnaire was used to analyze dietary preferences and health status. Polymerase chain reaction (PCR) was used to analyze polymorphisms at three common TAS2R38 loci (rs713598, rs1726866, and rs10246939). Results In our study population, 65.00% of individuals had medium sensitivity to the bitterness of PTC; in contrast, 20.94% were highly sensitive to PTC bitterness, and 14.06% were not sensitive. For the TAS2R38 gene, the PAV/PAV and PAV/AAI diplotypes were the most common (42.19% and 40.63%, respectively), followed by the homozygous AVI/AVI (8.75%) and PAV/AVI (5.00%) diplotypes. Conclusion There was a significant correlation between the sensitivity to PTC bitterness and sex, but there was no correlation between the common diplotypes of TAS2R38 and gender. Polymorphisms in the TAS2R38 gene were associated with the preference for tea, but not with one’s native place, BMI, health status, or other dietary preferences. There was no significant correlation between the perception of PTC bitterness and one’s native place, BMI, dietary preference, or health status. We hope to find out the relationship between PTC sensitivity and TAS2R38 gene polymorphisms and dietary preference and health status of Chinese population through this study, providing relevant guidance and suggestions for dietary guidance and prevention of some chronic diseases in Chinese population.

Background: The bitter taste receptor gene TAS2R38 is a member of the human TAS2R gene family. Polymorphisms in TAS2R38 affect the ability to taste the bitterness of phenylthiourea (PTC) compounds, thus affecting an individual's food preference and health status. Methods: We investigated polymorphisms in the TAS2R38 gene and the sensitivity to PTC bitterness among healthy Chinese college students in Hubei province. The association of TAS2R38 polymorphisms and PTC sensitivity with body mass index (BMI), food preference, and health status was also analyzed. A total of 320 healthy college students were enrolled (male: 133, female: 187; aged 18–23 years). The threshold value method was used to measure the perception of PTC bitterness, and a questionnaire was used to analyze dietary preferences and health status. Polymerase chain reaction (PCR) was used to analyze polymorphisms at three common TAS2R38 loci (rs713598, rs1726866, and rs10246939). Results: In our study population, 65.00% of individuals had medium sensitivity to the bitterness of PTC; in contrast, 20.94% were highly sensitive to PTC bitterness, and 14.06% were not sensitive. For the TAS2R38 gene, the PAV/PAV and PAV/AAI diplotypes were the most common (42.19% and 40.63%, respectively), followed by the homozygous AVI/AVI (8.75%) and PAV/AVI (5.00%) diplotypes. Conclusion: There was a significant correlation between the sensitivity to PTC bitterness and sex, but there was no correlation between the common diplotypes of TAS2R38 and gender. Polymorphisms in the TAS2R38 gene were associated with the preference for tea, but not with one's native place, BMI, health status, or other dietary preferences. There was no significant correlation between the perception of PTC bitterness and one's native place, BMI, dietary preference, or health status. We hope to find out the relationship between PTC sensitivity and TAS2R38 gene polymorphisms and dietary preference and health status of Chinese population through this study, providing relevant guidance and suggestions for dietary guidance and prevention of some chronic diseases in Chinese population. [ABSTRACT FROM AUTHOR]

Ability to perceive the bitter compound phenylthiocarbamide (PTC) is inherited via a dominant "taster" allele of the TAS2R38 gene, whereas inability is inherited via a recessive "non-taster" allele. This raises a question: Is the non-taster allele functionless, or does it mediate perception of compounds other than PTC? New evidence supports speculation that it is indeed functional. Associations between TAS2R38 mutations and bitter sensitivity to the tropical berry Antidesma bunius are the inverse of those PTC, suggesting that the non-taster allele enables perception to compounds in the fruit.

2-Substituted benzo- and naphthothiazoles have been conveniently prepared from the intramolecular cyclization of phenylthioureas and activated thiobenzanilides or the coupling of isothiocyanates with amines under mild conditions using N-bromosuccinimide/tetrabutylammonium bromide in 1,2-dimethoxyethane (DME) under ambient conditions. The reactions produce moderate to excellent yields with good functional group tolerance and avoid the use of harsh thermal conditions, corrosive reagents, halogenated solvents, toxic metal salts, and expensive metal catalysts, and are amenable to preparations on a gram-scale. [ABSTRACT FROM AUTHOR]

Reactions of 6-amino-2-methylquinolin-4-ol with salicylaldehyde, phthalic anhydride, phenyl isothiocyanate, and ammonium thiocyanate afforded 6-[(2-hydroxybenzylidene)amino]-2-methylquinolin-4-ol, 2-(4-hydroxy-2-methylquinolin-6-yl)-1H-isoindole-1,3(2H)-dione, N-(4-hydroxy-2-methylquinolin-6-yl)-N′-phenylthiourea, and 1-(4-hydroxy-2-methylquinolin-6-yl)thiourea, respectively. Heterocyclizations of the latter with ethyl bromoacetate and bromacetophenone led to the formation of 2-[(4-hydroxy-2-methylquinolin-6-yl)-imino]-1,3-thiazolidin-4-one and 2-methyl-6-[(4-phenyl-1,3-thiazol-2(3H)-ylidene)amino]quinolin-4-ol, respectively. [ABSTRACT FROM AUTHOR]

A study of the structural features and anti-inflammatory activity of 13-(N-arylaminocarbonyl)-9-methyl-11-thioxo-8-oxa-10,12-diazatricyclo[7.3.1.02,7]trideca-2,4,6-trienes and their N-phenyl-substituted derivatives revealed that these compounds exhibited high anti-inflammatory activity and could be rated as promising nonsteroidal anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Current breast cancer therapy does not always work optimally, and cases of resistance have been reported. Therefore, it is imperative to develop new effective drugs with minimal side effects through predictions of the epidermal growth factor receptor (EGFR) signalling pathway inhibition. Among chemicals with the potential as anticancer candidates for breast cancer are phenylthiourea derivatives. In this study, two phenylthiourea derivatives were synthesized: N- (4-methoxy)-benzoyl-N'-phenylthiourea and N-(4-trifluoromethyl)-benzoyl-N'-phenylthiourea. These compounds were docked with the EGFR receptor (code: 1M17.pdb) to predict their cytotoxic activity in silico using AutoDock tools. Furthermore, the microculture tetrazolium technique (MTT) was used to investigate in vitro cytotoxicity against MCF-7 cells. The in silico test revealed that the compounds N-(4-trifluoromethyl)-benzoyl-N'-phenylthiourea and N- (4-methoxy)-benzoyl-N'-phenylthiourea had a binding score of -8.2 and -7.3 kcal/mol, respectively, and the in vitro cytotoxic activity testing showed IC50 values of 0.37 mM and 0.38 mM, demonstrating significant EGFR inhibitory activity in MCF-7 cells. Therefore, it can be concluded that N-(4-trifluoromethyl)-benzoyl-N'-phenylthiourea has better cytotoxic activity than N-(4-methoxy)-benzoyl-N'-phenylthiourea. [ABSTRACT FROM AUTHOR]

Introduction: Urea- and thiourea-based compound has shown a potency to be further developed as anticancer compound. Objective: Another novel phenylthiourea analog (N-(2,4-dichloro) benzoyl-N'-phenylthiourea) was synthesized through Schotten-Baumann reaction followed by the assessment of its cytotoxic activity. Methods: N-(2,4-dichloro)benzoyl-N'-phenylthiourea was synthesized using N-Phenylthiourea and 2,4-dichlorobenzoyl chloride as starting materials. The reaction started at low temperature for 30 min followed by reflux for 8 h to yield target compound. Cytotoxicity assay was then performed against MCF-7, T47D, and Vero normal cell line. Results: The compound has been synthesized and its structure has been verified using infrared, 1H-nuclear magnetic resonance (NMR), 13C-NMR, various 2D NMR, and mass spectra. Furthermore, it is shown that the synthesized compound possesses better cytotoxicity profile than hydroxyurea. Conclusion: N-(2,4-dichloro)benzoyl-N'-phenylthiourea is a potential thiourea analog as anticancer agent, albeit further research is needed. [ABSTRACT FROM AUTHOR]

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

Common TAS2R38 taste receptor gene variants specify the ability to taste phenylthiocarbamide (PTC), 6-n-propylthiouracil (PROP) and structurally related compounds. Tobacco smoke contains a complex mixture of chemical substances of varying structure and functionality, some of which activate different taste receptors. Accordingly, it has been suggested that non-taster individuals may be more likely to smoke because of their inability to taste bitter compounds present in tobacco smoke, but results to date have been conflicting. We studied three cohorts: 237 European-Americans from the state of Georgia, 1,353 European-Americans and 2,363 African-Americans from the Dallas Heart Study (DHS), and 4,973 African-Americans from the Dallas Biobank. Tobacco use data was collected and TAS2R38 polymorphisms were genotyped for all participants, and PTC taste sensitivity was assessed in the Georgia population. In the Georgia group, PTC tasters were less common among those who smoke: 71.5% of smokers were PTC tasters while 82.5% of non-smokers were PTC tasters (P = 0.03). The frequency of the TAS2R38 PAV taster haplotype showed a trend toward being lower in smokers (38.4%) than in non-smokers (43.1%), although this was not statistically significant (P = 0.31). In the DHS European-Americans, the taster haplotype was less common in smokers (37.0% vs. 44.0% in non-smokers, P = 0.003), and conversely the frequency of the non-taster haplotype was more common in smokers (58.7% vs. 51.5% in non-smokers, P = 0.002). No difference in the frequency of these haplotypes was observed in African Americans in either the Dallas Heart Study or the Dallas Biobank. We conclude that TAS2R38 haplotypes are associated with smoking status in European-Americans but not in African-American populations. PTC taster status may play a role in protecting individuals from cigarette smoking in specific populations.

The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 and bitter taste perception of phenylthiocarbamide. Yet, due to overlaps in specificities across receptors, such associations with a single TAS2R locus are uncommon. Therefore, to investigate more complex associations, we examined taste responses to six structurally diverse compounds (absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine) in a sample of the Caucasian population. By sequencing all bitter receptor loci, inferring long-range haplotypes, mapping their effects on phenotype variation, and characterizing functionally causal allelic variants, we deciphered at the molecular level how a subjects' genotype for the whole-family of TAS2R genes shapes variation in bitter taste perception. Within each haplotype block implicated in phenotypic variation, we provided evidence for at least one locus harboring functional polymorphic alleles, e.g. one locus for sensitivity to amarogentin, one of the most bitter natural compounds known, and two loci for sensitivity to grosheimin, one of the bitter compounds of artichoke. Our analyses revealed also, besides simple associations, complex associations of bitterness sensitivity across TAS2R loci. Indeed, even if several putative loci harbored both high- and low-sensitivity alleles, phenotypic variation depended on linkage between these alleles. When sensitive alleles for bitter compounds were maintained in the same linkage phase, genetically driven perceptual differences were obvious, e.g. for grosheimin. On the contrary, when sensitive alleles were in opposite phase, only weak genotype-phenotype associations were seen, e.g. for absinthin, the bitter principle of the beverage absinth. These findings illustrate the extent to which genetic influences on taste are complex, yet arise from both receptor activation patterns and linkage structure among receptor genes.

2-Substituted benzo- and naphthothiazoles have been conveniently prepared from the intramolecular cyclization of phenylthioureas and activated thiobenzanilides or the coupling of isothiocyanates with amines under mild conditions using N-bromosuccinimide/tetrabutylammonium bromide in 1,2-dimethoxyethane (DME) under ambient conditions. The reactions produce moderate to excellent yields with good functional group tolerance and avoid the use of harsh thermal conditions, corrosive reagents, halogenated solvents, toxic metal salts, and expensive metal catalysts, and are amenable to preparations on a gram-scale.

The biosynthesis of pyoverdine, the major siderophore of Pseudomonas aeruginosa , is a well-organized process involving a discrete number of enzyme-catalyzed steps. The final step of this process involves the PvdP tyrosinase, which converts ferribactin into pyoverdine. Thus, inhibition of the PvdP tyrosinase activity provides an attractive strategy to interfere with siderophore synthesis to manage P. aeruginosa infections. Here, we report phenylthiourea as a non-competitive inhibitor of PvdP for which we solved a crystal structure in complex with PvdP. The crystal structure indicates that phenylthiourea binds to an allosteric binding site and thereby interferes with its tyrosinase activity. We further provide proofs that PvdP tyrosinase inhibition by phenylthiourea requires the C-terminal lid region. This provides opportunities to develop inhibitors that target the allosteric site, which seems to be confined to fluorescent pseudomonads, and not the tyrosinase active site. Furthermore, increases the chances to identify PvdP inhibitors that selectively interfere with siderophore synthesis. • The structure of the pyoverdine synthesizing tyrosinase, PvdP, provides a novel target for developing antibiotics. • Phenylthiourea has been discovered as a non-competitive inhibitor with a unique mechanism of inhibition. • The structure of the copper-enzyme establishes the role of this metal as a cofactor. • Inhibition of PvdP interferes with the production of pyoverdine thus impairing the iron uptake ability in Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

Recently, 10 2-mercaptobenzo[ d ]imidazole (2-MBI) compounds (1 – 10) were synthesized. Although all 2-MBI compounds are tyrosinase inhibitors that inhibit mushroom tyrosinase at extremely low concentrations (IC 50 values: 20–740 nM) and effectively inhibit the browning of apples, to our knowledge, no studies have determined whether 2-MBI compounds inhibit mammalian tyrosinase. Mammalian tyrosinase is different from mushroom tyrosinase in its distribution within the cell and has structural characteristics that are different from mushroom tyrosinase in amino acid sequence and in the presence of a quaternary structure. Thus, the effect of the 10 2-MBI compounds on mammalian tyrosinase activity was investigated in B16F10 cells. Six compounds (1 – 6) exhibited stronger intracellular tyrosinase inhibition than that of kojic acid and phenylthiourea (PTU), which are known to be the most potent tyrosinase inhibitors; their strong tyrosinase inhibitory activity robustly inhibited intracellular melanin production in B16F10 cells. None of the tested 2-MBI compounds exhibited appreciable cytotoxicity in HaCaT and B16F10 cells. To confirm the anti -melanogenic efficacy of the 2-MBI compounds in vivo , a zebrafish embryo model was used. At concentrations 100 times lower than kojic acid, most 2-MBI compounds demonstrated much stronger depigmentation efficacy than that of kojic acid, and three 2-MBI compounds (2 – 4) showed depigmentation activity similar to or more potent than that of PTU, resulting in nearly pigment-free zebrafish embryos. These results suggest that 2-MBI compounds may be potential therapeutic agents for hyperpigmentation-related disorders. [Display omitted] • 2-Mercaptobenzo[ d ]imidazole (2-MBI) derivatives (1 – 10) greatly inhibited mammalian cell tyrosinase in B16F10 cells. • Four 2-MBI derivatives inhibited intracellular melanin production in B16F10 cells more potently than kojic acid and PTU. • Depigmentation experiments of 2-MBI derivatives using zebrafish embryos resulted in pigment-free zebrafish embryos. • These 2-MBI derivatives did not exhibit significant cytotoxicity in B16F10 cells and HaCaT cells at concentrations ≤20 μM. • These results suggest that 2-MBI derivatives may be potential therapeutic agents for hyperpigmentation-related disorders. [ABSTRACT FROM AUTHOR]

Tyrosinase-related protein 1 (TYRP1) is one of the three human melanogenic enzymes involved in the biosynthesis of melanin, a pigment responsible for the color of the skin, hair, and eyes. It shares high sequence identity with tyrosinase, but has two zinc ions in its active site rather than two copper ions as in tyrosinase. Typical tyrosinase inhibitors do not directly coordinate to the zinc ions of TYRP1. Here, we show, from an X-ray crystal structure determination, that phenylthiourea, a highly potent tyrosinase inhibitor, does neither coordinate the active site zinc ions, but binds differently from other structurally characterized TYRP1-inhibitor complexes. Its aromatic ring is directed outwards from the active site, apparently as a result from the absence of polar oxygen substituents that can take the position of water molecules bound in the active site. The compound binds via hydrophobic interactions, thereby blocking substrate access to the active site.

Background: Olfactory dysfunction has been reported to be involved in Parkinson's disease (PD) pathogenesis. However, gustatory dysfunction in PD has not been evaluated as in-depth as olfactory dysfunction. We reviewed the previously published studies regarding gustatory function in PD patients and suggested the possibility that gustatory dysfunction may also be associated with PD., Methods: MEDLINE, Cochrane Library, Embase, and PubMed databases were searched for studies evaluating gustatory function in PD patients. We used the standardized mean difference and a 95% confidence interval (CI) as the effect analysis index regarding the taste strip test. The relative risk and 95% CI were used as the effect analysis index for the questionnaires and propylthiouracil (PTU)/phenylthiocarbamide (PTC) perception test. Statistical heterogeneity was assessed using forest plots, Cochran's Q, and the I 2 statistic; heterogeneity was considered high when I 2 was over 75%. Publication bias was assessed by funnel plots and the Egger bias test., Results: We identified 19 articles that reported the results of gustatory function tests in PD patients and healthy controls. Most of these studies used various gustatory tests, including taste strips, questionnaires, taste solutions, PTU/PTC perception tests, and electrogustometry, and reported significantly lower gustatory function in PD patients than in the controls. However, several articles reported contradictory results., Conclusions: Based on these studies, gustatory dysfunction is closely related to PD. However, the number of studies and enrolled subjects was small, and a unified gustatory function test was lacking. Therefore, further studies with larger populations and normalized gustatory function tests are needed., (© 2023 ARS-AAOA, LLC.)

A novel phenylthiourea modified Mn-Anderson polyoxometalate, [N(C 4 H 9 ) 4 ] 3 [MnMo 6 O 18 {(OCH 2 ) 3 CNHCSNHPh}{(OCH 2 ) 3 CNH 2 }] ( 1 ) has been synthesized and characterized by IR, NMR, UV–Vis spectroscopy, thermogravimetric, electrochemical and single-crystal X-ray diffraction analysis. Structural analysis reveals that compound 1 crystallizes in the orthorhombic crystal system, space group Pcab with a  = 17.7477(9) Å, b  = 33.6245(16) Å, c  = 32.322(2) Å, V  = 19288.7(19) Å 3 and Z  = 8. Noticeably, the asymmetric POM cluster with terminal modification could be connected through H-bonding interactions of C H⋯O to form an infinite supramolecular chain. Furthermore, the adjacent 1D chains are linked by H-bonding interactions of N H⋯O to generate a 2D supramolecular layer. [ABSTRACT FROM AUTHOR]

• Prepartion of a new spirocompound containing thiourea group. • X-ray diffraction, FT-IR and FT-Raman were applied to solve the molecular structure. • DFT calculations were performed to confirm experimental data. • Study of MEP, NBO, NLO, thermodynamic properties and Hirshfeld surfaces. A new spirocompound containing thiourea group 1-((2,4-dioxo-1,5-dioxaspiro[5.5]undecan-3-ylidene)methyl)-3-phenylthiourea (DMP) was designed and obtained. The compound (DMP) was confirmed using the single X-ray diffraction, 1H NMR and 13C NMR, IR, Raman, MS and UV–Vis. The DFT calculations of molecular structure, infrared and Raman spectroscopy and electronic transition were performed using the two different levels of B3LYP/cc-pVDZ/ and B3LYP/6–311G(d, p). The theoretical results match with the experimental ones. The gap energy of HOMO and LUMO of DMP was 3.88 eV. The DMP is thermally stable up to 200 °C according to the data obtained from TG analysis. Finally, the Mulliken population analysis, Hirshfeld surfaces analysis, MEP, NLO and NBO of DMP were discussed. A new spirocompound containing thiourea group have been obtained and characterized by IR and Raman, NMR (1H and 13C), MS, UV–Vis spectra and single crystal X-ray crystallography. Its experimental and theoretical vibrational frequencies and electronic spectra have been investigated using the DFT/B3LYP method with different basis sets (6–311G(d, p) and cc-pVDZ). In addition, MEP, NBO, NLO and thermodynamic properties have also been studied. [Display omitted] [ABSTRACT FROM AUTHOR]

The influence of growth regulators and nitrogenous compounds on in vitro bulblet formation and growth was studied in two hybrids of Lilium. Bulbscales isolated from pre-cooled bulbs of hybrids Rosato and Marco Polo were used. The basal portion with plate (5 × 6 mm) of inner bulbscales was cultured on Murashige and Skoog (MS) medium containing 0.5 or 1 mg/dm3 naphthaleneacetic acid (NAA) and/or benzyladenine (BA). The presence of NAA (0.5 mg per dm3) showed higher explant regeneration, producing about three bulblets per explant as compared to control. About four bulblets per explant were produced at both concentrations of BA. The bulblets with significantly higher fresh weight were obtained on medium containing NAA. Approximately a three-fold increase of bulblet fresh weight was observed with all the concentrations of TDZ in both cultivars. The bulblets cultured with nitrogenous compounds after attaining the size of 14-16 cm flowered during the second year of the growing period without any phenotypic variations.

The structure and analgesic activity of 13-(N-aryl(N,N-diethyl)-aminocarbonyl)-9-methyl-11-thioxo-8-oxa-10,12-diazatricyclo[7.3.1.02,7]trideca-2,4,6-trienes and their 10-N-phenyl derivatives were studied. The studied compounds were shown to possess analgesic activity with low acute toxicity. [ABSTRACT FROM AUTHOR]

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN 2 S 2 -based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus . Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.

A new method for preparing allobetulin via thermal rearrangement of betulin in the presence of phenylthiourea without using acidic reagents was found. [ABSTRACT FROM AUTHOR]

Detection of substances tasting bitter to humans occurs in diverse organisms including the social amoeba Dictyostelium discoideum. To establish a molecular mechanism for bitter tastant detection in Dictyostelium, we screened a mutant library for resistance to a commonly used bitter standard, phenylthiourea. This approach identified a G-protein-coupled receptor mutant, grlJ-, which showed a significantly increased tolerance to phenylthiourea in growth, survival and movement. This mutant was not resistant to a structurally dissimilar potent bitter tastant, denatonium benzoate, suggesting it is not a target for at least one other bitter tastant. Analysis of the cell-signalling pathway involved in the detection of phenylthiourea showed dependence upon heterotrimeric G protein and phosphatidylinositol 3- kinase activity, suggesting that this signalling pathway is responsible for the cellular effects of phenylthiourea. This is further supported by a phenylthiourea-dependent block in the transient cAMP-induced production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in wild-type but not grlJ- cells. Finally, we have identified an uncharacterized human protein c-aminobutyric acid (GABA) type B receptor subunit 1 isoform with weak homology to GrlJ that restored grlJ- sensitivity to phenylthiourea in cell movement and PIP3 regulation. Our results thus identify a novel pathway for the detection of the standard bitter tastant phenylthiourea in Dictyostelium and implicate a poorly characterized human protein in phenylthiourea-dependent cell responses. [ABSTRACT FROM AUTHOR]

The transcription factor NF-κB is a pivotal mediator of chronic inflammatory and autoimmune diseases. Based on our previously published dual EGFR/NF-κB inhibitors, we designed and synthesized new thiourea quinazoline derivatives that retained only the NF-κB inhibitory activity. Several congeners displayed a strong suppression of NF-κB activity in a reporter gene assay, yet low cytotoxicity, and were further evaluated in differentiated macrophage-like THP-1 cells. The compounds exhibited a strong inhibition of IL-6 and, less potently, of TNFα release, which was accompanied by a selective induction of macrophage cell death. The mode of action was investigated with a selected inhibitor, 18, revealing that the translocation of p65/RelA to the nucleus but not its release from the IκB complex was inhibited. Eventually, 18 was identified as the first small molecule inhibitor affecting only the phosphorylation of p65-Ser468 but not of Ser536, which may be causally related to the retention of NF-κB in the cytoplasm. Altogether, our novel NF-κB inhibitors seem applicable for the suppression of cytokine release and the additional selective depletion of activated macrophages in various inflammatory diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2 H )-yl)-3-phenylthiourea ( 2 ) was prepared and reacted with various hydrazonoyl halides 3a - h, α-haloketones 5a - d , 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b , which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a - h, 3-phenyl-4-arylthiazoles 6a - d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b , respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC 50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC 50 = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.