Proapoptotic effects of halogenated bis-phenylthiourea derivatives in cancer cells.

New halogenated thiourea derivatives were synthesized via the reaction of substituted phenylisothiocyanates with aromatic amines. Their cytotoxic activity was examined in in vitro studies against solid tumors (SW480, SW620, PC3), a hematological malignance (K-562), and normal keratinocytes (HaCaT). Most of the compounds were more effective against SW480 (1a, 3a, 3b, 5j), K-562 (2b, 3a, 4a), or PC3 (5d) cells than cisplatin, with favorable selectivity. Their anticancer mechanisms were studied by Annexin V-fluorescein-5-isothiocyanate apoptosis, caspase-3/caspase-7 assessment, cell cycle analysis, interleukin-6 (IL-6) release inhibition, and reactive oxygen species (ROS) generation assay. Thioureas 1a, 2b, 3a, and 4a were the most potent activators of early apoptosis in K-562 cells, and substances 1a, 3b, 5j triggered late-apoptosis or necrosis in SW480 cells. This proapoptotic effect was proved by the significant increase of caspase-3/caspase-7 activation. Cell cycle analysis revealed that derivatives 1a, 3a, 5j increased the number of SW480 and K-562 cells in the sub-G1 and/or G0/G1 phases, and one evoked cycle arrest at the G2 phase. The most potent thioureas inhibited IL-6 cytokine secretion from PC3 cells and both colon cancer cell lines. Apoptosis-inducing compounds also increased ROS production in all tumor cell cultures, which may enhance their anticancer properties.

From EGFR kinase inhibitors to anti-inflammatory drugs: Optimization and biological evaluation of (4-(phenylamino)quinazolinyl)-phenylthiourea derivatives as novel NF-κB inhibitors.

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.

Variations in the TAS2R38 gene among college students in Hubei.

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.

Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives.

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 CuN2S2-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.

Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety.

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(2H)-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 (IC50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC50 = 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.

Residue analysis, dissipation patterns of chlorfenapyr, diafenthiuron and their corresponding metabolites in tea trees, and dietary intake risk assessment.

BACKGROUND: Recently, chlorfenapyr and diafenthiuron have been widely used to prevent and control diseases and pests in tea production. However, rare studies have investigated the dissipation patterns of chlorfenapyr, diafenthiuron and their metabolites simultaneously in tea matrices. Here, we established an analytical method to investigate the degradation patterns of five target compounds in tea shoots and made tea samples. Moreover, the dietary intake risk assessment of chlorfenapyr-diafenthiuron mixture among Chinese populations was evaluated based on the supervised field experiment. RESULTS: The mean recoveries of the primary analytes at five spiking levels were between 95.6% and 112.6% in tea shoots and made tea, respectively, and the values of RSD (relative standard deviation) were lower than 9.7% for all the target analytes. The field trial results showed that the half-lives of chlorfenapyr and diafenthiuron based on the residue definition were 10.0-12.4 days and 4.3-5.9 days, respectively, in tea shoots. For the dietary intake risk assessment, the risk quotient (RQ) values in made tea ranged from 30.4% to 73.9% at the pre-harvest interval of 14 days, which were significantly less than 100%. CONCLUSION: The accuracy and precision of the developed method were satisfied by the measurement requirements according to the validation results. The dynamic dissipation experiments suggested that diafenthiuron was much easier to dissipate than chlorfenapyr. Moreover, the existence of tralopyril made the half-life of chlorfenapyr significantly increase, indicating that practical application of chlorfenapyr should take careful consideration of its metabolite. Finally, the potential chronic dietary risks of the chlorfenapyr-diafenthiuron mixture to human communities were within the acceptable range. © 2022 Society of Chemical Industry.

Further Insights into the Oxidative Pathway of Thiocarbonyl-Type Antitubercular Prodrugs: Ethionamide, Thioacetazone, and Isoxyl.

A chemical activation study of the thiocarbonyl-type antitubercular prodrugs, ethionamide (ETH), thioacetazone (TAZ), and isoxyl (ISO), was performed. Biomimetic oxidation of ethionamide using H2O2 (1 equiv) led to ETH-SO as the only stable S-oxide compound, which was found to occur in solution in the preferential form of a sulfine (ETH═S═O vs the sulfenic acid tautomer ETH-S-OH), as previously observed in the crystal state. It was also demonstrated that ETH-SO is capable of reacting with amines, as the putative sulfinic derivative (ETH-SO2H) was supposed to do. Unlike ETH, oxidation of TAZ did not allow observation of the mono-oxygenated species (TAZ-SO), leading directly to the more stable sulfinic acid derivative (TAZ-SO2H), which can then lose a SOxH group after further oxidation or when placed in a basic medium. It was also noticed that the unstable TAZ-SO intermediate can lead to the carbodiimide derivative as another electrophilic species. It is suggested that TAZ-SOH, TAZ-SO2H, and the carbodiimide compound can also react with NH2-containing nucleophilic species, and therefore be involved in toxic effects. Finally, ISO showed a very complex reactivity, here assigned to the coexistence of two mono-oxygenated structures, the sulfine and sulfenic acid tautomers. The mono- and dioxygenated derivatives of ISO are also highly unstable, leading to a panel of multiple metabolites, which are still reactive and likely contribute to the toxicity of this prodrug.

Validation of the Waterless Empirical Taste Test (WETT®).

The sense of taste is rarely assessed quantitatively outside of a limited number of academic and industrial laboratories, despite its role in influencing nutrition, the flavor of foods and beverages, and protection against ingestion of spoiled and toxic foodstuffs. This dearth reflects, in part, practical limitations of most taste tests, most notably their reliance on liquid stimuli for stimulus presentation or rinsing. In this study, a novel portable taste test that requires neither liquid tastants nor liquid rinses is described and validated within a clinic population. This test, termed the Waterless Empirical Taste Test (WETT®), uses stimuli that are embedded in pads of monometer cellulose located on disposable plastic strips applied to the tongue's surface. The test-retest and split-half reliability coefficients of the WETT® were 0.92 and 0.88, respectively. These respective coefficients for sucrose, NaCl, citric acid, caffeine, and MSG were 0.82 and 0.80, 0.78 and 0.77, 0.56 and 0.73, and 0.84 and 0.84. The WETT® exhibited comparable, in some cases higher, sensitivity than two comparison taste tests, the Whole Mouth Taste Test and the Taste Quadrant Taste Test, to age, sex, etiology (head trauma vs. upper respiratory infections), and phenylthiocarbamide (PTC) taste ability. This study demonstrates that a taste test that does not require liquids can be as reliable and sensitive as more traditional liquid-based taste tests to clinical alterations in taste function.

Searching for novel hydrogen sulfide donors: The vascular effects of two thiourea derivatives.

The gasotransmitter hydrogen sulfide (H2S) is involved in the regulation of the vascular tone and an impairment of its endogenous production may play a role in hypertension. Thus, the administration of exogenous H2S may be a possible novel and effective strategy to control blood pressure. Some natural and synthetic sulfur compounds are suitable H2S-donors, exhibiting long-lasting H2S release; however, novel H2S-releasing agents are needed to improve the pharmacological armamentarium for the treatment of cardiovascular diseases. For this purpose, N-phenylthiourea (PTU) and N,N'-diphenylthiourea (DPTU) compounds have been investigated as potential H2S-donors. The thioureas showed long-lasting H2S donation in cell free environment and in human aortic smooth muscle cells (HASMCs). In HASMCs, DPTU caused membrane hyperpolarization, mediated by activation of KATP and Kv7 potassium channels. The thiourea derivatives promoted vasodilation in rat aortic rings, which was abolished by KATP and Kv7 blockers. The vasorelaxing effects were also observed in angiotensin II-constricted coronary vessels. In conclusion, thiourea represents an original H2S-donor functional group, which releases H2S with slow and long lasting kinetic, and promotes typical H2S-mediated vascular effects. Such a moiety will be extremely useful for developing original cardiovascular drugs and new chemical tools for investigating the pharmacological roles of H2S.

Development of phenylthiourea derivatives as allosteric inhibitors of pyoverdine maturation enzyme PvdP tyrosinase.

Infections caused by Pseudomonas aeruginosa become increasingly difficult to treat because these bacteria have acquired various mechanisms for antibiotic resistance, which creates the need for mechanistically novel antibiotics. Such antibiotics might be developed by targeting enzymes involved in the iron uptake mechanism because iron is essential for bacterial survival. For P. aeruginosa, pyoverdine has been described as an important virulence factor that plays a key role in iron uptake. Therefore, inhibition of enzymes involved in the pyoverdine synthesis, such as PvdP tyrosinase, can open a new window for the treatment of P. aeruginosa infections. Previously, we reported phenylthiourea as the first allosteric inhibitor of PvdP tyrosinase with high micromolar potency. In this report, we explored structure-activity relationships (SAR) for PvdP tyrosinase inhibition by phenylthiourea derivatives. This enables identification of a phenylthiourea derivative (3c) with a potency in the submicromolar range (IC50 = 0.57 + 0.05 µM). Binding could be rationalized by molecular docking simulation and 3c was proved to inhibit the bacterial pyoverdine production and bacterial growth in P. aeruginosa PA01 cultures.

Sublethal effects of methylthio-diafenthiuron on the life table parameters and enzymatic properties of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae).

The diamondback moth (DBM), Plutella xylostella (L.), is a major pest affecting cruciferous vegetables, and seriously affects the quality and yield of these vegetables. Diafenthiuron is a traditional thiourea-based insecticide, but it is rarely used to control pests on cruciferous vegetables due to its phytotoxicity on these vegetables under high temperature and light conditions. Thus, there is an ongoing need for more effective pesticides that can be used on cruciferous vegetables, possibly including new formulations of diafenthiuron. A new thiourea insecticide, methylthio-diafenthiuron, is intended to optimize the structure of diafenthiuron not only to preserve its insecticidal bioactivity but also to overcome its phytotoxicity to cruciferous vegetables, aiming to control insect pests on cruciferous vegetables. In this study, we compared the toxicity of methylthio-diafenthiuron to some frequently used insecticides on the third-instar larvae of DBM. The parental pupal duration was significantly longer under the treatment than in the control, but the pupal weight, fecundity, and hatching rate significantly decreased. By studying the changes in three detoxifying enzymes within 72 h after treatment with a sublethal concentration, the activity of CarE and ODM in the treatment group significantly increased at first and then decreased. In addition, methylthio-diafenthiuron clearly inhibited three kinds of ATPases in the DBM and significantly reduced the eclosion rate of the pupae. This research provides valuable information for the assessment and rational application of methylthio-diafenthiuron for the control of pests on cruciferous vegetables.

Phenylthiourea Binding to Human Tyrosinase-Related Protein 1.

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.

Detection thresholds for quinine, PTC, and PROP measured using taste strips.

PURPOSE: In clinical practice, when ability to perceive bitter taste is studied, quinine is preferred to phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) as taste stimulus, because many subjects are genetically non-tasters for PTC/PROP. However, it is poorly known how sensitive anterior (front) and posterior (back) parts of the tongue are to different bitter tastants that are detected by different bitter taste receptors (TAS2Rs). In the present study, we aimed to characterize sensitivity to bitter taste at front and back parts of tongue. METHODS: We measured thresholds for quinine, PTC, and PROP using the "taste strips", employing seven concentrations of each stimulus both at front and back parts of tongue in 203 healthy participants (56% females, mean age 28 years). RESULTS: Our data confirmed the hypothesis that the inability to perceive quinine was less frequent than the inability to perceive PTC and PROP: People can still perceive the bitter taste of quinine even if they are "non-tasters" for PROP/PTC. As expected, strong correlations between PTC and PROP thresholds were observed. Interestingly, correlations between thresholds for quinine and PTC/PROP also emerged. Overall, the detection thresholds were lower when measured at front part of the tongue. CONCLUSIONS: Our data suggest that determining taster status for quinine using paper "taste strips", applied to front part of the tongue, represents a suitable method for the screening for ageusia for bitter taste.

Bitter Fruit: Inverse Associations Between PTC and Antidesma bunius Perception.

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.

Taste Perception of Antidesma bunius Fruit and Its Relationships to Bitter Taste Receptor Gene Haplotypes.

It was shown more than 40 years ago that the ability to perceive the bitterness of the fruit of the Antidesma bunius tree is inversely correlated with the ability to perceive the well-studied bitter tastant phenylthiocarbamide (PTC). To determine if variants of the TAS2R38 gene, which encodes the PTC taste receptor, or variants in any of the other TAS2R bitter or TAS1R sweet receptor genes account for Antidesma taste perception, we recruited an independent subject sample and examined associations between these taste receptor gene haplotypes and Antidesma perception. Consistent with previous findings, almost none of our subjects who reported Antidesma juice as bitter was a PTC "responder" by previous definitions (i.e. a PTC taster). In our study, of the 132 individuals who perceived PTC as bitter, 15 perceived Antidesma as bitter, although these 15 subjects had very weak bitterness perception scores. Examination of TAS2R38 gene haplotypes showed that, of the subjects who perceive Antidesma as bitter, all carried at least one copy of the TAS2R38 AVI (PTC non-taster) haplotype. However, 86 subjects carried at least one AVI haplotype and failed to perceive Antidesma as bitter. No other TAS2R or TAS1R gene variants showed an association with Antidesma bitter, sweet, or sour perception. Our results show that TAS2R38 haplotypes are associated with differential perception of Antidesma berry juice bitterness, and that all those who perceive this bitterness carry at least one AVI haplotype. This indicates that the AVI haplotype is necessary for this perception, but that additional variable factors are involved.

Synthesis, characterization, antioxidant, antidiabetic, anticholinergic, and antiepileptic properties of novel N-substituted tetrahydropyrimidines based on phenylthiourea.

In the presence of trifluoroacetic acid, on the basis of three-component condensation of phenylthiourea with its salicylaldehyde and methyl-3-oxobutanoate, an efficient method for the synthesis of 1-(4-(2-hydroxyphenyl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone (I) has been worked out. These novel N-substituted tetrahydropyrimidines based on phenylthiourea showed good inhibitory action against acetylcholinesterase (AChE), α-glycosidase, and human carbonic anhydrase (hCA) isoforms I and II. K i values of AChE enzyme were in the range of 0.48 to 7.46 nM. The hCA I and II were effectively inhibited by the compounds, with K i values in the range of 502.44 to 923.11 nM for hCA I and 400.32 to 801.57 nM for hCA II, respectively. The antioxidant activity of the novel N-substituted tetrahydropyrimidines based on phenylthiourea was investigated by using different in vitro antioxidant assays; including 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Cu 2+  and Fe 3+ reducing activities.

Preference for tap, bottled, and recycled water: Relations to PTC taste sensitivity and personality.

This study investigated people's preferences for different water sources and factors that predict such preferences using a blind taste test. Water preferences of 143 participants for one name-brand bottled water, one groundwater-sourced tap water, and one indirect potable reuse (IDR) water were assessed. For predictors of water preference, we measured each participant's PTC taste sensitivity and assessed two personality traits (Neuroticism, Openness to Experience). We also explored participants' descriptions of each water source. Results indicate a preference for water treated with Reverse Osmosis (RO) (bottled and IDR water) over groundwater-sourced water, which had higher pH levels and lower concentrations of Ca and HCO3-. PTC taste sensitivity did not predict preferences, while Openness to Experience and Neuroticism predicted preference for IDR water. Positive relations between Openness to Experience and preferences for bottled and IDR water were moderated by gender and were stronger among females. Participants described water primarily by its taste and texture. Findings suggest that (1) tap water treated by RO is equally preferable to some bottled water, (2) personality traits may affect water preferences, and (3) prior findings of gender differences in preferences for bottled water may reflect personality characteristics. Efforts to increase acceptance for sustainable water alternatives, such as IDR, may be more successful by assuring consumers about taste and addressing personality traits that encourage or inhibit use.

Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception.

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.

Disubstituted 4-Chloro-3-nitrophenylthiourea Derivatives: Antimicrobial and Cytotoxic Studies.

4-Chloro-3-nitrophenylthioureas 1⁻30 were synthesized and tested for their antimicrobial and cytotoxic activities. Compounds exhibited high to moderate antistaphylococcal activity against both standard and clinical strains (MIC values 2⁻64 µg/mL). Among them derivatives with electron-donating alkyl substituents at the phenyl ring were the most promising. Moreover, compounds 1⁻6 and 8⁻19 were cytotoxic against MT-4 cells and various other cell lines derived from human hematological tumors (CC50 ≤ 10 µM). The influence of derivatives 11, 13 and 25 on viability, mortality and the growth rate of immortalized human keratinocytes (HaCaT) was observed.

Variation in the Ability to Taste Bitter Thiourea Compounds: Implications for Food Acceptance, Dietary Intake, and Obesity Risk in Children.

The ability to taste bitter thiourea compounds, such as phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), is inherited. Polymorphisms in the bitter-taste receptor TAS2R38 explain the majority of phenotypic variation in the PROP phenotype. It has been hypothesized that the PROP phenotype is a marker for perception of a variety of chemosensory experiences. In this review, we discuss studies that have investigated the relationship between bitter-taste response and dietary behaviors and chronic health in children. Investigators have hypothesized that children who are PROP tasters have lower liking and consumption of bitter foods, such as cruciferous vegetables. Additionally, several studies suggest that children who are unable to taste PROP (i.e., nontasters) like and consume more dietary fat and are prone to obesity. The relationship between the PROP phenotype and obesity is influenced by multiple confounders, including sex, food access, ethnicity, and socioeconomic status. Future studies that adjust for these variables are needed.