Substituted Thiourea Derivatives Research Articles

3,3-Disubstituted 1-acylthioureas as ionophores for Pb(II)-ion selective electrodes: physical and chemical characterization of the sensing membranes

Solid-state Pb(II) ion selective electrodes were developed, which are based on 3,3-disubstituted 1-acylthioureas as ionophores and use PVC membranes. 1-Benzoyl, 1-(2-furoyl), 3,3-diethyl and 3,3-diphenyl were the substituent groups on the thioureide core. The analytical parameters for the constructed electrodes were studied. The electrodes based on 3,3-diethyl substituted thiourea derivatives showed better analytical response to Pb(II) ions with suitable sensitivity and an average lifetime of more than 30 days. Cu(II), Hg(II) and Ag(I) ions were interfering species during Pb(II) detection. Scanning electron microscopy and atomic force microscopy micrographs of the activated sensing membranes revealed morphological changes, which have been associated with the performance of the sensors. The studies have suggested that the detection of few large size particles or aggregates at the membrane surface are responsible for inadequate functioning of the prepared electrodes. This pattern was mainly observed for the sensing membranes based on 3,3-diphenyl groups as substituents and is related to unfavorable steric and electronic factors. Furthermore, X-ray photoelectron spectroscopy profiles S2p and Pb4f supported chemically the analytical response displayed for the four membrane systems. The X-ray photoelectron spectroscopy results combined with scanning electron microscopy and atomic force microscopy studies shed light on the working mechanism of the studied electrodes.

Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives.

Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Compounds 1–5, 8, and 9 were highly cytotoxic against human colon (SW480, SW620) and prostate (PC3) cancer cells, and leukemia K-562 cell lines (IC50 ≤ 10 µM), with favorable selectivity over normal HaCaT cells. The derivatives exerted better growth inhibitory profiles towards selected tumor cells than the reference cisplatin. Compounds incorporating 3,4-dichloro- (2) and 4-CF3-phenyl (8) substituents displayed the highest activity (IC50 from 1.5 to 8.9 µM). The mechanisms of cytotoxic action of the most effective thioureas 1–3, 8, and 9 were studied, including the trypan blue exclusion test of cell viability, interleukin-6, and apoptosis assessments. Compounds reduced all cancerous cell numbers (especially SW480 and SW620) by 20–93%. Derivatives 2 and 8 diminished the viability of SW620 cells by 45–58%. Thioureas 1, 2, and 8 exerted strong pro-apoptotic activity. Compound 2 induced late apoptosis in both colon cancer cell lines (95–99%) and in K-562 cells (73%). All derivatives acted as inhibitors of IL-6 levels in both SW480 and SW620 cells, decreasing its secretion by 23–63%.

Sequential One-Pot Synthesis of 2-Aminothiazoles Using Corresponding Ketones: Insights into Their Structural Features

2-Aminothiazoles have been synthesized by a one-pot, two-step sequential procedure in solution state which does not involve the isolation of intermediates. It involves α-halogenation of corresponding precursor ketones followed by condensation with substituted thiourea derivatives. All the products were analyzed by IR, NMR, mass spectral techniques and four of them were evaluated crystallographically. One of them crystallizes in the triclinic crystal system with space group P , while, all the other compounds crystallize in the monoclinic crystal system in two different space groups viz. P21/c and P21/n. The modified 2-aminothiazole core did not show any change in the intermolecular interaction. The N-H…N interaction predominates over other interactions forming centrosymmetric head to head dimer with the neighboring atoms. This feature is observed in all the molecules except N-(4-(4-bromophenyl)-3-(2,5-dimethylphenyl)thiazol-2(3H)-ylidene)-2,5-dimethylaniline.

Theoretical investigation of structure, anticancer activity and molecular docking of thiourea derivatives

Quantum chemical computations and in silico biological evaluation of three substituted thiourea derivatives namely (4-nitrophenyl)thiourea (NPT), (3,5-dimethylphenyl) thiourea (DMPT) and 1,3-di-o-tolylthiourea (DTTU) are described in this study. Spectroscopic properties and vibrational analysis of these derivatives have been characterized experimentally through Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectral techniques and theoretically using density functional theory (DFT) method employing B3LYP functional implemented with the 6-311++G(d,p) basis set. Electronic properties such as molecular electrostatic potential (MEP) and HOMO–LUMO analysis were executed to identify the most reactive site and also to identify the charge transfer takes place within the molecules. Besides, the natural bond orbital (NBO) analysis was carried out to explain the delocalization of charge takes place within the molecule due to intramolecular interactions. Molecular docking and molecular dynamics simulation studies verified the inhibitory nature of the title compounds against BRAF (V600E) protein kinase. Assessment of ADMET properties along with the drug-likeness parameter has exposed good drug-like behaviour of the title compounds. Furthermore, through in silico approaches, the thiourea derivatives under study were evaluated for their antineoplastic activity and were shown to possess potential anticancer activity.

Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives.

Novel ibuprofen derivatives 1-19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2-19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1H-, and 13C-NMR spectroscopic techniques. The synthetic molecules 1-19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC50 = 2.96-178μM as compared to the standard thiourea (IC50 = 21.32 ± 0.22μM). Out of nineteen, thirteen derivatives 2-4, 6, 7, 9, 11-15, 17, and 18 demonstrated remarkable inhibitory activity with IC50 values of 2.96 ± 1.11 to 16.1 ± 1.07μM, compound 5 exhibited moderate inhibition with IC50 value of 37.3 ± 0.41μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure-activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.

Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 µM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.

Synthesis of carboxylic dithiocarbamic anhydride and substituted thiourea derivatives in water

The use of water as a solvent has sometimes benefits such as improving reactivities and selectivities, simplifying work-up procedures, and environmentally benign. Many carboxylic dithiocarbamic anhydride products are valuable building blocks in heterocycles and natural products. Here we present a simple one-pot synthesis of carboxylic dithiocarbamic anhydride by condensation of amines, carbon disulfide, acyl halide, or acetic anhydride in water. We obtained a variety of biologically important acyl dithiocarbamate derivatives in 82–93% yields in 10–30 min. This procedure can be used for the synthesis of thioureas from dithiocarbamates. Here, the sequential, one-pot three-component reaction of amines, carbon disulfide, and isothiocyanates provides unsymmetrical substituted thioureas in 81–91% yields.

The complexing ability of n-substituted thiourea derivatives as chelating ligands in the reaction with PdCl2

The complexation reactions of N-substituted thiourea derivatives with PdCl2 have been investigated in the present work. The functionally substituted thiourea derivatives are found to be effective chelating agents, in which the nature of substituents has a significant impact to the compositions and structures of complexes. Thus, (N-pyridine-2-yl)thioureas in the interaction with PdCl2 form two types of complexes in the molar ratio of M:L 1:1 and 1:2, in which they act as S,N-bidentate ligands coordinated to the palladium ion by thione sulphur and the nitrogen atom of the pyridine ring. The reaction of N-allylthioureas with PdCl2 in the equimolar ratio results in formation of the π-complexes where the ligands are coordinated by the thione sulphur and the C=C double bond of the allylic moiety. The preparative methods for the synthesis of this type of complexes have been developed. The composition of the products synthesized and the ligands coordination mode have been determined by elemental analysis and 1H NMR spectroscopy. Furthermore, the structure of compounds 4, 5 has been confirmed by the X-ray diffraction study. The biomedical studies have proven that the complex compounds 5 and 6 in vitro have the cytostatic and cytotoxic activity against tumour HeLa cells.

ChemInform Abstract: Gold Nanoparticle Catalyzed Intramolecular C—S Bond Formation/C—H Bond Functionalization/Cyclization Cascades.

AbstractThe catalyst system is applied to the oxidative cyclization of substituted thiourea derivatives to afford the corresponding benzothiazole derivatives (II).

Cytotoxicity effects of alkoxy substituted thiourea derivatives towards Acanthamoeba sp.

In this study, the effort was to design and synthesize five new members of alkoxy substituted thiourea derivatives (3a–3e) featuring general formula of A-ArC(O)NHC(S)NHAr-D in which A represents the methoxy group and D as –OCnH2n+1 (alkoxyl group, where n=6,7,8,9, and 10) have been successfully designed, prepared, characterized, and evaluated for anti-amoebic activities. They were spectroscopically characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared (FT-IR) spectroscopy, and Ultraviolet–visible (UV–vis) spectroscopy analysis. In turn, they were used to investigate the cytotoxicity effect on Acanthamoeba sp. at their IC50 values and membrane permeability. Compounds 3a and 3b revealed to have good activity towards Acanthamoeba sp. compared to other compounds of 3c, 3d, and 3e. The observation under fluorescence microscopy by AOPI (Acridine-orange/Propidium iodide) staining indicated that treated amoeba cells by 3a–3e show loss of their membrane permeability.

Synthesis and Anti Hiv-1 Reverse Transcriptase Evaluation of A Series of N-Mono Substituted Thiourea Derivatives

Thirteen kinds of N-monosubstituted thioureas have been synthesized from various primary amines through three differ- ent methods. The chemical structures of all the compounds have been characterized by the various spectral analyses. Four of them were evaluated for the anti-HIV-1 activity. The results showed that compound 1b, showing the IC 50 = 29.7 (μg/ mL) to the strain of ROD of HIV-1, CC 50 > 50 (μg/mL), SI (selectivity index) > 2, was the best one among the test com- pounds. As for other compound 1a, 1c and 1d, the SI of them was less than 1, which means that these compounds might be toxic at the therapeutic level. Both the steric, electronic and topologic descriptors of the molecules were calculated to assist understanding the basic relationship between the structure and the biological activity. The docking result of 1c with HIV-1 reverse transcriptase (HIV-1 RT, PDB ID: 2HNZ) showed that there were still more unexploited rooms in the active site of the binding pocket of HIV-1 RT with compounds 1c

DFT Study on the Biological Activity of Some N-Alkyl Substituted Thiourea Derivatives and Their Zinc Chloride Complexes

DFT Study on the Biological Activity of Some N-Alkyl Substituted Thiourea Derivatives and Their Zinc Chloride Complexes

Corrosion Inhibition Effects of Some New Synthesized N-Aroyl-N\ -Aryl thiourea Derivatives for Carbon Steel in Sulfuric Acid Media

This research includes the synthesis of some new N-Aroyl-N -Aryl thiourea derivatives namely: N-benzoyl-N -(p-aminophenyl) thiourea (STU1), N-benzoyl-N -(thiazole) thiourea (STU2), N-acetyl-N ` -(dibenzyl) thiourea (STU3). The series substituted thiourea derivatives were prepared from reaction of acids with thionyl chloride then treating the resulted with potassium thiocyanate to affored the corresponding N-Aroyl isothiocyanates which direct reaction with primary and secondary aryl amines, The purity of the synthesized compounds were checked by measuring the melting point and Thin Layer Chromatography (TLC) and their structure, were identified by spectral methods [FTIR, 1 H-NMR and 13 C-NMR].These compounds were investigated as a corrosion inhibitor for carbon steel in 1M H2SO4 solution using weight loss, potentiostatic polarization methods; the obtained results showed that the substituted thioureas retard both cathodic and anodic reactions in acid media, by virtue of adsorption on the carbon steel surface. This adsorption obeyed Langmuir’s adsorption isotherm. The inhibition efficiency of (STU1-3) is ranging between (60-95)%. By using different (STU3) derivative concentration and temperature, the carbon steel corrosion rate was decreased with increasing (STU3) concentration and the highest inhibition efficiency reach to 98.5% by using 5×10 -4 M (STU3) concentration at 338 K, the inhibition efficiency increases with increasing temperature in the range of (308-338)K.

Synthesis, Spectroscopic Characterization, Crystal structure, Antimicrobial and In Vitro Hemolytic Studies of Some Novel Substituted Thiourea Derivatives

A series of N,N′-disubstituted thioureas, [R–CONHCSNH–R′] where (R = thiophenyl, furonyl, phenyl and R′ = 4-sulphonamido phenyl, pyrimidine-2yl, thiazole-2yl, 3-nitro phenyl, 2-nitro-4-chloro phenyl, 2-chloro-4-nitro phenyl, 2-methoxy-4-nitro phenyl, and 6-phenyl-1,3,5-triazinyl were synthesized, characterized and screened for their antimicrobial activities. The structures of synthesized compounds were established by elemental analysis and spectroscopic techniques (FT-IR, 1H NMR, and 13C NMR). Single crystal study on compounds 1a and 1c have been done. The compound 1a crystallizes in monoclinic space group Cc, with a = 15.2974(5) A, b = 11.7766(4) A, c = 8.1059(3) A, α = 90°, β = 106.31(3)°, γ = 90° and Z = 4 molecules per unit cell, where as compound 1c crystallizes in orthorhombic space group Pbca, with a = 7.6307(6) A, b = 11.3895(9) A, c = 24.121(2) A, α = β = γ = 90° and Z = 8 molecules per unit cell. All the compounds were tested for their inhibitory activities against four human pathogen bacteria and three fungal strains. The screening data revealed that five compounds showed moderate to good activity whereas one of the compound 1k displayed excellent activity. In vitro hemolytic activity of the compounds has shown them to be nontoxic in nature. Eleven disubstituted thiourea compounds have been synthesized and characterized by elemental analysis, spectroscopic techniques (FT-IR, 1H NMR, and 13C NMR) and single crystal study on two of compounds has been done to understand the proper structural features of the compounds. All the compounds have been screened for their antimicrobial activity; out of them two have shown promising activity against the bacteria and fungi used.

ChemInform Abstract: Highly Efficient and Catalyst‐Free Synthesis of Substituted Thioureas in Water.

A highly efficient and catalyst-free method for the synthesis of substituted thiourea derivatives is presented. The synthesis is performed through the reaction of thiazolidine-2-thiones with various amines in water. A sound number of thioureas with both unsymmetrical and symmetrical architectures have been obtained in good to excellent yields.

Highly efficient and catalyst-free synthesis of substituted thioureas in water

A highly efficient and catalyst-free method for the synthesis of substituted thiourea derivatives is presented. The synthesis is performed through the reaction of thiazolidine-2-thiones with various amines in water. A sound number of thioureas with both unsymmetrical and symmetrical architectures have been obtained in good to excellent yields.

Synthesis and anticonvulsant activity of substituted thiourea derivatives

Synthesis and anticonvulsant activity of substituted thiourea derivatives

ChemInform Abstract: Preferred Conformations of Some 2-Pyridyl Substituted Thiourea Derivatives. A Reinvestigation of NMR Spectral Data.

A previous report involving 1 H nmr spectra of some 1-phenyl and 1-benzoyl 3(2-pyridyl)thioureas was reinvestigated and found to be incorrect. Analysis of the data permits the designation of preferred conformations for these systems

ChemInform Abstract: A Concise Synthesis of Substituted Thiourea Derivatives in Aqueous Medium.

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A Concise Synthesis of Substituted Thiourea Derivatives in Aqueous Medium

An efficient method for the synthesis of symmetrical and unsymmetrical substituted thiourea derivatives by means of simple condensation between available building blocks such as amines and carbon disulfide in aqueous medium is presented. This protocol works smoothly with aliphatic primary amines to afford various di- and trisubstituted thiourea derivatives. The present method is also useful in synthesizing various substituted 2-mercapto imidazole heterocycles. This method proceeds through a xanthate (amino dithiol deivative) intermediate, unlike isothiocyanate as in an earlier known method.