Phenylthiourea Research Articles

Synthesis and Anticancer Activity of Thiadiazole Containing Thiourea, Benzothiazole and Imidazo[2,1-b][1,3,4]thiadiazole Scaffolds.

A great array of nitrogen-containing heterocyclic rings were being extensively explored for their functional versatility in the field of medicine, especially in anticancer research. 1,3,4- thiadiazole is one of such heterocyclic rings with promising anticancer activity against several cancer cell lines, inhibiting diverse biological targets. The 1,3,4-thiadiazole, when equipped with other heterocyclic scaffolds, has displayed enhanced anticancer properties. The thiourea, benzothiazole, imidazo[2,1,b][1,3,4]-thiadiazoles are such potential scaffolds with promising anticancer activity. A new series of 5-substituted-1,3,4-thiadiazoles linked with phenyl thiourea, benzothiazole and 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized and tested for invitro anticancer activity on various cancer cell lines. The National Cancer Institute's preliminary anticancer screening results showed compounds 4b and 5b having potent antileukemic activity. Compound 4b selectively showed 32 percent lethality on Human Leukemia-60 cell line. The docking studies of the derivatives on aromatase enzyme (Protein Data Bank: 3S7S) have shown reversible interactions at the active site with good docking scores comparable to Letrozole and Exemestane. Furthermore, the selected derivatives were tested for anticancer activity on HeLa cell line based on the molecular docking studies. Compounds 4b and 5b showed effective inhibition equivalent to Letrozole. These preliminary biological screening studies have given positive anticancer activity for these new classes of derivatives. An additional research study like the mechanism of action of the anticancer activity of this new class of compounds is necessary. These groundwork studies illuminate a future pathway for research of this class of compounds enabling the discovery of potent antitumor agents.

The synthesis of heterocyclic derivatives of phenyl(benzoyl) thiourea

The synthesis of heterocyclic derivatives of phenyl(benzoyl) thiourea

Efficient construction of C–C bonds from aryl halides/aryl esters with arylboronic acids catalysed by palladium(II) thiourea complexes

A new set of palladium(II) complexes comprising phenyl(thiazolyl)thiourea ligands have been successfully synthesized and characterized with the aid of analytical as well as spectral (IR, UV–visible and NMR) methods. A distorted square‐planar geometry with N^S coordination mode of thiourea ligands in the new palladium complexes was corroborated by single‐crystal X‐ray diffraction methods. Interestingly, the palladium(II) thiourea complexes showed the highest catalytic activity with 0.1 mol% catalyst loading in Suzuki–Miyaura cross‐coupling reactions utilizing a range of aryl bromides/unactivated aryl chlorides with arylboronic acids as coupling partners in aqueous–organic media. Syntheses of diaryl ketones using aryl esters and arylboronic acids as coupling partners were also achieved with low catalyst loading within 20 h. The potential of our catalyst was demonstrated by its wide substrate scope, low catalyst loadings and high isolated yield. Moreover, the influences of key parameters like solvent, base, temperature and catalyst loading were also investigated.

Action of Metarhizium brunneum (Hypocreales: Clavicipitaceae) Against Organophosphate- and Pyrethroid-Resistant Aedes aegypti (Diptera: Culicidae) and the Synergistic Effects of Phenylthiourea.

Dengue, yellow fever, Zika, and chikungunya arboviruses are endemic in tropical countries and are transmitted by Aedes aegypti. Resistant populations of this mosquito against chemical insecticides are spreading worldwide. This study aimed to evaluate the biological effects of exposure of pesticide-sensitive Ae. aegypti larvae (Rockefeller) to conidia of the entomopathogen, Metarhizium brunneum, laboratory strains ARSEF 4556 and V275, and any synergistic activity of phenylthiourea (PTU). In addition, to investigate the nature of any cross-resistance mechanisms, these M. brunneum strains were tested against the Rockefeller larvae and two temephos- and deltamethrin-resistant wild mosquito populations from Rio de Janeiro. Treatment of Rockefeller larvae with 106 conidia/ml of ARSEF 4556 and V275 fungal strains resulted in significant decreased survival rates to 40 and 53.33%, respectively (P < 0.0001), compared with untreated controls. In contrast, exposure to 104 or 105 conidia/ml showed no such significant survival differences. However, the addition of PTU to the conidia in the bioassays significantly increased mortalities in all groups and induced a molt block. Experiments also showed no differences in Ae. aegypti mortalities between the fungal treated, wild pesticide-resistant populations and the Rockefeller sensitive strain. The results show the efficacy of M. brunneum in controlling Ae. aegypti larvae and the synergistic role of PTU in this process. Importantly, there was no indication of any cross-resistance mechanisms between Ae. aegypti sensitive or resistant to pesticides following treatment with the fungi. These results further support using M. brunneum as an alternative biological control agent against mosquito populations resistant to chemical insecticides.

Designing and performance evaluation of polyelectrolyte multilayered composite smart coatings

This work reports the synthesis of polyelectrolyte microcapsules and its effect on the anti-corrosion performance of polymeric coating applied on steel substrates. In situ polymerization technique was used for the synthesis of monolayered urea formaldehyde microcapsules loaded with linalyl acetate (MLMCs). These capsules can be broken upon mechanical stress, such as scratches or other forms of mechanical damage. To enhance corrosion protection, Phenylthiourea (PTU), a molecule sensitive to pH, was loaded between consecutive polyelectrolytes layers of polyethylenimine (PEI) and sulfonated polyether ether ketone (SPEEK) build on the surface of MLMCs using the layer by layer technique. This polyelectrolyte layered microcapsules (PMCs) carry linalyl acetate in its core and phenylthiourea entrapped between the outer layers. Both MLMCs and PMCs, in concentration of 6 wt%, were dispersed in the epoxy resin and the resulting formulation was used to coat steel plates. Experimental findings showed that epoxy coatings reinforced with PMCs demonstrate better thermal, self-healing and anti-corrosion properties. This improved performance can be attributed to the release of polymer healing and corrosion inhibiting species from the PMCs. The epoxy coatings modified with PMCs can serve as self healing coating for corrosion protection of steel parts used, for example, in the oil and gas industry.

In Vivo Effects of A Pro-PO System Inhibitor on the Phagocytosis of Xenorhabdus Nematophila in Galleria Mellonella Larvae.

Xenorhabdus nematophila is a Gram-negative bacterium symbiont of the entomopathogen nematode Steinernema carpocapsae whose immunosuppressive properties over host’s immune response have been thoroughly investigated. In particular, live X. nematophila actively impairs phagocytosis in host’s hemocytes through the secretion of inhibitors of eicosanoids synthesis. In this article we have investigated the cell surface structural features of X. nematophila responsible for the elusion from phagocytosis. To this end we have studied the uptake of heat-killed (hk), fluorescein isothiocyanate (FITC)-labeled X. nematophila by phagocytes from both a host insect and a mammalian species. In vitro dead X. nematophila passively resists engulfment by insect hemocytes without impairing the phagocytosis machinery whereas, unexpectedly, in vivo a significant phagocytosis of dead X. nematophila was observed. X. nematophila in vivo phagocytosis was increased by the co-injection of the specific inhibitor of pro-phenoloxidase (PO) system phenylthiourea (PTU), even if these effects were not observed in in vitro tests. Furthermore, biochemical modifications of X. nematophila cell wall implement in vivo phagocytosis, suggesting that this bacterium avoid phagocytosis because the ligand of phagocytic receptors is somehow buried or disguised in the cell wall. Finally, dead X. nematophila escapes engulfment even by human phagocytes suggesting that X. nematophila could be a useful model to investigate escape from phagocytosis by mammalian macrophages.

The Role of Tyrosinase in the Time Course of Light‐Induced Cone Contraction in the Goldfish Retina

Dopamine is an important modulator of light‐adaptation in the vertebrate retina. Many teleosts regulate the amount of light incident on the retina through retinomotor movements (RMMs), that include changes in cone and rod length. In the dark, cones elongate and rods contract. In the light, rods elongate and cones contract. It is thought that RMMs are regulated by the release of dopamine in the light from tyrosine hydoxylase‐containing interplexiform cells. However, RMMs are not lost when these dopaminergic retinal neurons are ablated by injection of the neurotoxin 6‐hydroxydopamine (6‐OHDA). A potential alternate source of dopamine in the retina is the retinal pigmented epithelium, due to the activity of tyrosinase.Adult goldfish (C. auratus) were treated with a specific inhibitor of tyrosinase, phenylthiourea (PTU), by placing them in tank water containing 0.2mM PTU for 48 hours. Control and fish treated with PTU were placed in dark for 1hr or light (&gt;100 lux) for 1 hr, or after 1hr darkness then exposed to varying durations of light (1.5 – 30 min). Another set of fish were given intraocular injections of 50μg 6‐OHDA twice on the first 2 days of a 10‐day time course and then subjected to dark/light treatments in the presence or absence of PTU. Fish were sacrificed, eyes removed and fixed in glutaraldehyde. Retinas were isolated and sliced using a razor blade. Cones were labeled by anti‐zpr1 (ZIRC, Eugene, OR) and cone length determined using confocal microscopy. Differences between means (in all case n=10 eyes) were assessed for statistical significance using ANOVA and, when applicable, Tukey's multiple comparison test.In fully light‐ or dark‐adapted conditions, retinas treated with PTU, 6‐OHDA or 6‐OHDA + PTU were indistinguishable from controls, However, both PTU and 6‐OHDA treatment slowed light‐induced cone contraction over the first 15 min of light. This delay was even greater when 6‐OHDA and PTU were combined. In the dark cones were elongated (115 ± 7 μm) and, under control conditions (no PTU, no 6‐OHDA) reached 80% (66 ± 2 μm) of maximum contraction (55 ± 3 μm) after 7.5 min light exposure. In the presence of either PTU or after 6‐OHDA treatment, cone length at 7.5min was significantly (p&lt;0.001) longer (75 ± 3 μm and 79 ± 2 μm, respectively) and was longer still when PTU and 6‐OHDA were combined (85 ± 1 μm).These results suggest that inhibition of tyrosinase (via PTU) or loss of neuronal dopamine (via 6‐OHDA) affects the early phase of light‐induced cone contraction. That neither treatment prevented full contraction may indicate that these treatments did not fully eliminate dopamine signaling in the retina, or that light‐induced cone contraction may also involve other mechanisms independent of dopamine.Support or Funding InformationThis work was supported by NSERC Discovery Grant awarded to WHB.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Synthesis, Characterization and Biological Analysis of Some Novel Complexes of Phenyl Thiourea Derivatives with Copper

Introduction: Copper is a very important metal because all forms of life require copper metals an essential micronutrient. Various biological processes, directly or indirectly are dependent on copper metal. Methods: Copper soaps are used as fungicides, bacteriosides, herbicides and insecticides. Copper complexes including heterocyclic compounds have attracted our attention in a magnificent way because of its utility in catalysis and biological functions. Their mechanism of synthesis, characterization and structural insight, are crucial for comprehending the criteria of the bonding and electronic interactions between the proximate metal center and chelating atoms. But still, there is a need to explore some of more biological properties for their wide applicability and significant usage in multiple fields because it is an untapped area with potentially tremendous value. Hence, in this paper, we report the synthesis and characterization of transition metal complex of N/S ligand by chromatographic, FT-IR, NMR, ESR, elemental analysis, conductometric and magnetic moment measurements. Results: The synthesized metal complexes namely copper palmitate with 4-nitrophenylthiourea and copper palmitate with 4-methoxyphenylthiourea were successfully investigated for biological activities against fungi Candida albicans and Trichoderma harzinum. Based on the results, we pronounced biocidal activities of the novel complexes. Conclusion: It is concluded that the activity of nitro phenylthiourea complex has greater antifungal activity than methoxy phenylthiourea complex against these test fungi. We can conclude that the antifungal activity of these complexes varies according to the nature of the groups attached to the ligands.

Synthesis, structures, drug-likeness, in vitro evaluation and in silico docking on novel N-benzoyl-N′-phenyl thiourea derivatives

In this paper, we have synthesized a series of N-benzoyl-N′-phenyl thiourea derivatives and characterized them by FTIR, elemental analysis, NMR, and X-ray single crystal diffraction. Intermolecular interactions were shown via NH⋯O, NH⋯S, CH⋯O, CH⋯S hydrogen bonds and π⋯π interactions in crystal. Furthermore, antifungal activity of these compounds was determined against Fusarium graminearum, Botryosphaeria ribis, Botryosphaeria berengriana and Cercospora brassicicola P. Hennings. In order to screen anti-cancer drugs, molecular docking was performed by using Hsp90 protein and target ligands (1∼8). Finally, parameters drug-likeness, ADME properties, toxicity effects (mutagenic, tumorigenic, irritant, and reproductive) and drug scores were calculated for evaluating bioavailability of thioureas. The results show that compound 4 has good antifungal activity compared with standard drugs and compound 5 has the potential to become an HSP90 inhibitor. More importantly, all synthesized compounds had good drug-likeness properties.

Inhibition of Mild Steel Corrosion in Acid Medium

Since inhibition is the simplest mechanism used for mitigating the corrosion of metals and alloys, particularly in acidic environments, the present work aims to investigate the inhibiting effect of N-benzyl-N′-phenyl thiourea (BPTU) and N-cyclohexyl-N′-phenyl thiourea (CPTU) on mild steel corrosion in 0.1M HCl medium using the Tafel extrapolation technique. Tafel experiments were conducted with ±250 mV vs. rest potential (RP) in steps of 20 mV from the cathodic side for recording the corrosion currents, and then, the Tafel plot of potential vs. current was drawn for determining the corrosion current density (icorr). The linear polarization method was also used for validating the Tafel results. It was performed by polarizing the specimen with ±20 mV vs. RP in steps of 5 mV, and the corrosion currents were noted. The plot of potential vs. current was drawn for calculating icorr. The study reveals that both BPTU and CPTU act as anodic inhibitors for mild steel in the HCl medium, and good inhibition efficiency (>97%) was evidenced from both the compounds even at elevated temperatures. The study also reveals that the investigated compounds get adsorbed quickly on the steel surface, following Temkin’s adsorption isotherm. The kinetic parameters obtained from the study indicated that the inhibition was governed by a chemisorption mechanism and the presence of inhibitors substantially reduced the metal dissolution in the studied temperature range. The investigation shows that there was a good correlation between the Tafel extrapolation and linear polarization results

The activity of phenoloxidase in haemolymph plasma is not a predictor of Lymantria dispar resistance to its baculovirus.

Host innate immunity is one of the factors that determines the resistance of insects to their entomopathogens. In the research reported here we studied whether or not phenoloxidase (PO), a key enzyme in the melanogenesis component of humoral immunity of insects, plays a role in the protection of Lymantria dispar larvae from infection by L. dispar multiple nucleopolyhedrovirus. We studied two types of viral infection: overt and covert. The following lines of investigation were tested: i) the intravital individual estimation of baseline PO activity in haemolymph plasma followed by virus challenging; ii) the specific inhibition of PO activity in vivo by peroral treatment of infected larvae with phenylthiourea (PTU), a competitive inhibitor of PO; iii) the evaluation of PO activity in the haemolymph plasma after larval starvation. Starvation is a stress that activates the covert infection to an overt form. All of these experiments did not show a relationship between PO activity in haemolymph plasma of L. dispar larvae and larval susceptibility to baculovirus. Moreover, starvation-induced activation of covert viral infection to an overt form occurred in 70 percent of virus-carrying larvae against the background of a dramatic increase of PO activity in haemolymph plasma in the insects studied. Our conclusion is that in L. dispar larvae PO activity is not a predictor of host resistance to baculovirus.

Base-promoted synthesis of N-arylbenzamides by N-benzoylation of dimethylphenylthioureas

An efficient synthesis of 10 N-arylbenzamides was achieved by N-benzoylation of N,N-dimethyl-( N′-phenyl)thioureas with 4-substituted benzoyl chlorides in dimethylacetamide in the presence of K2CO3. The features of this method include good yields, short reaction times and broad substrate scope. This work showed that arylthiourea derivatives can be alternative and useful starting materials for the preparation of N-arylbenzamides.

In VitroInhibition of Polyphenol Oxidase Activity by Insecticides and Allelochemicals inClostera anastomosis(Lepidoptera: Notodontidae) Larvae and Poplar Trees

Abstract Clostera anastomosis (L.) (Lepidoptera: Notodontidae) is an important leaf-feeding insect of poplars, Populus spp. (Salicaceae) in China. As part of a continuing search for environmentally friendly insecticides for this pest, we compared the in vitro inhibition of polyphenol oxidase (PPO) activity by 21 insecticides and allelochemicals in C. anastomosis and poplar trees (populous × euramericana ‘NanLin895′). The results showed that three inhibitors (quercetin, phenyl thiourea, and phoxim) can strongly inhibit PPO activity in both C. anastomosis and poplars, but the inhibitory degree with each was significantly different. Our results further showed that three inhibitors had a certain dose relationship with the PPO activity in C. anastomosis and poplars. The I50 values (50% inhibitory concentration) of three chemicals (quercetin, phenyl thiourea, and phoxim) were estimated as 14.17, 0.18, and 127.67 μM for C. anastomosis and as 0.34, 0.15, and 0.21 mM for poplars, respectively. These results will ...

An Ultrasensitive and Selective Probe for Ratiometric Determination and Removal of Hg2+

New methods are desired not only to quantitatively determine but also effectively remove mercury from environmental sources, because mercury is a highly hazardous and ubiquitous pollutant with bioaccumulative properties. Herein, we developed an ultrasensitive and highly selective ratiometric electrochemical probe for accurate determination and quick removal of mercury from water. Phenyl thiourea (PT) was designed as a specific recognition element for Hg2+, and detection was achieved by selective binding and reduction of Hg2+ on PT-functionalized electrode. Meanwhile, HS-DNA-MB (5′-MB-AGGAGGAGGAGGGAGGAGGG-SH-3′) was designed as an inner reference element, providing a built-in correction for quantitative determination of Hg2+. The present probe shows high sensitivity for Hg2+ detection in a broad dynamic range from 1 nM to 1.3 μM, with relatively low detection limit of 0.12 nM (0.024 ppb). This electrochemical probe was successfully applied for determination of Hg2+ in environmental water. More interestingly, it was also used to effectively remove Hg2+ from Huangpu River water within just 7 min without further separation.

P-Coumaric Acid Potently Down-regulates Zebrafish Embryo Pigmentation: Comparison ofin vivoAssay and Computational Molecular Modeling with Phenylthiourea

<i>p</i>-Coumaric Acid Potently Down-regulates Zebrafish Embryo Pigmentation: Comparison of<i>in vivo</i>Assay and Computational Molecular Modeling with Phenylthiourea

β-Stereoselective Mannosylation Using 2,6-Lactones.

β-Stereoselective mannosylation using donors bearing the 2,6-lactone moiety is described. In general, glycosylation is a nucleophilic substitution reaction between an alcoholic nucleophile and a sugar moiety containing a leaving group at the anomeric position. Owing to stereoelectronic effects, the reaction tends to proceed via an SN1 mechanism to afford α-glycosides. We found that the introduction of a 2,6-lactone bridge can circumvent the competing SN1 reaction, affording β-glycosides with stereoinversion via SN2(-like) mechanisms. Glycosyl trichloroacetimidates are particularly efficient when activated by a combined catalyst of AuCl3 and 3,5-bis(trifluoromethyl)phenyl thiourea. In addition, the product stereoselectivity was highly dependent on the concentration of the reaction. Moreover, even when the reaction proceeds via an SN1 mechanism, the corresponding glycosyl cation appears to present sterically a β-directing nature. Overall, 2,6-lactones were promising structures for achieving β-mannosylations.

Studies on the effects of thiourea and its derivatives doped—Hybrid/zirconium nanocomposite based sol-gel coating for the corrosion behaviour of aluminum metal

Abstract The present work examines the effects of thiourea and its derivatives on corrosion behaviour of hybrid/zirconium (Hy/Zr) nanocomposite based sol-gel coatings. The hybrid sols were prepared by hydrolysis and condensation of 3-glycidoxypropyltrimethoxysilane (GPTMS), tetramethoxysilane (TMOS) and tetra- n -propoxyzirconium (TPOZ) in acidic solution. Thiourea (TU), N -phenylthiourea (PTU), N -methylthiourea (MTU) and N -allylthiourea (ATU) which act as networking agents were doped seperately into the Hy/nano-Zr sol and were self-assembled over aluminum substrates. Fourier transform infrared (FT-IR) spectra, Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray Spectroscopy (EDX) analyses were employed to investigate structure and morphologies of various coatings. The corrosion protection ability of these sol-gel coatings were evaluated by electrochemical impedance studies (EIS) and potentiodynamic polarization (PP) measurements in 3.5% NaCl medium. The results showed that among the various thiourea derivatives, MTU-doped-Hy/Zr nanocomposite based sol-gel coating exhibited better corrosion protection than the undoped Hy/nano-Zr, TU-doped-Hy/Zr, PTU-doped-Hy/Zr and ATU-doped-Hy/Zr nanocomposite coatings. The enhanced corrosion protection was mainly due to the presence of Hy/nano-Zr particles and electron donating nature of MTU which lead to the formation of densely packed layer functioning as a significant physical barrier against the attack of corrosive ions over the aluminum metal surface.

Electrochemical Corrosion of Low Carbon Steel in a Hydrochloric Acid Medium

Inhibition is one of the mechanisms used for mitigating the metallic corrosion, particularly in an acid environment. The present work aims to investigate the inhibiting effect of N-benzyl-N/-phenyl thiourea (BPTU) on the corrosion of low carbon steel in a 0.1 M hydrochloric acid (HCl) solution using a Tafel extrapolation and linear polarization techniques. The study reveals that BPTU acts as an excellent anodic inhibitor for low carbon steel in a HCl solution. The protective efficiency of the compound was found to be more than 97% even at higher temperatures. The study demonstrated that BPTU gets adsorbed on the steel surface, following Temkin’s adsorption isotherm and the inhibition is controlled by a chemisorption mechanism. The investigation shows that the results obtained from the Tafel extrapolation and linear polarization techniques for the corrosion of mild steel in HCl medium were in good agreement. The influence of temperatures and concentrations of BPTU on the corrosion of low carbon steel are also examined in the present work

Anthelmintic and antibacterial screening of a new series of N-[4-(4-nitrophenoxy)phenyl]-4-(substituted)-1,3-thiazol-2-amines

A series of N-[4-(4-nitrophenoxy)phenyl]-4-(substituted)-1,3-thiazol-2-amines was synthesized. Structural elucidation was accomplished by 1H NMR, 13C NMR, IR, and elemental analyses of synthesized compounds. The title compounds were derived from 4-(4-nitrophenoxy)phenyl thiourea, which is the key intermediate in the synthesis of nitroscanate, an anthelmintic drug. Among the synthesized compounds, N-[4-(4-nitrophenoxy)phenyl]-4-(4-fluorophenyl)-1,3-thiazol-2-amine and N-[4-(4-nitrophenoxy)phenyl]-4-(4-methoxyphenyl)-1,3-thiazol-2-amine exhibited potent anthelmintic and antibacterial activities.

Expression of the bitter receptor T2R38 in pancreatic cancer: localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule.

T2R38 belongs to the family of bitter receptors and was initially detected in cells of the oral cavity. We now describe expression of T2R38 in tumor cells in patients with pancreatic cancer and in tumor-derived cell lines. T2R38 is localized predominantly intracellular in association with lipid droplets, particularly with the lipid droplet membrane. The receptor can be activated by the bona fide ligand for T2R38, phenylthiourea (PTU), and by N-acetyl-dodecanoyl homoserine (AHL-12), a quorum sensing molecule of Pseudomonas aeruginosa, the latter is the only known natural ligand for T2R38. In response to PTU or AHL-12, key transcription factors are activated including phosphorylation of the MAP kinases p38 and ERK1/2, and upregulation of NFATc1. Moreover, we found increased expression of the multi-drug resistance protein 1 (also known as ABCB1), a transmembrane transporter molecule, participating in shuttling of a plethora of drugs, such as chemotherapeutics or antibiotics. In conclusion, our data indicate a new, additional function of the taste receptor T2R38 beyond sensing ‘bitter’. Moreover, because T2R38 can be stimulated by a bacteria-derived signaling molecule the receptor could link microbiota and cancer.