In search of potent urease inhibitor indole analogues (1-22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1-22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed.Communicated by Ramaswamy H. Sarma.
Thiourea derivatives (1-38) were synthesized and evaluated for their urease inhibition potential. The synthetic compounds showed a varying degree of in vitro urease inhibition with IC50 values 5.53 ± 0.02-91.50 ± 0.08 μM, most of which are superior to the standard thiourea (IC₅₀ = 21.00 ± 0.11 μM). In order to ensure the mode of inhibition of these compounds, the kinetic study of the most active compounds has been carried out. Most of these inhibitors were found to be mixed-type of inhibitors, except compounds 13 and 30 which were competitive, while compound 19 was identified as non-competitive inhibitor with Ki values between 8.6 and 19.29 μM.
High nutrient loading in aquatic environment has become the main causative of harmful algae blooms (HABs) in water resources particularly pond, lake and river. HABs are mostly dominated by microalgae derived from the group of blue-green algae which are capable of releasing harmful toxins. Therefore, this study aims to investigate the inhibitory effects of thiourea derivatives on the growth of such blue-green algae. Thiourea derivatives have been proven to exhibit antifungal and antibacterial effects. However, there is still limited study had been conducted on the effect of thiourea derivatives toward blue-green algae species in recent years. In this research, a species of blue-green algae from Kenyir Lake, Terengganu, Malaysia was successfully isolated using morphological characters and molecularly identified as Synechoccus elongatus. Four new thiourea derivative compounds were also successfully synthesised. The compounds were designed with variation on different R-substitution group and characterised using Nuclear Magnetic Resonance (NMR) to confirm their molecular structure. Those compounds were characterised as 1-Benzyl-3-(3,5-dimethoxy-benzoyl)-thiourea (C1), 1-(3-Chloro-benzyl)-3-(3,5-dimethoxy-benzoyl)-thiourea (C2), 1-(3,5-Dimethoxy-benzoyl)-3-(3-methyl-benzyl)-thiourea (C3) and 1-(3,5-Dimethoxy-benzoyl)-3-(3-trifluoromethyl-benzyl)-thiourea (C4). For the inhibition assessment,S. elongatus were treated with C1-C4 for 5 day at concentration of 2, 5, 10 and 20 μg/ml, respectively. C3 compound showed the highest inhibition percentage with 98% of inhibition after 5 days treatment. By using Bradford method, protein extraction of S. elongatus was conducted at the highest inhibition percentage. Protein concentration of treated species was observed with 3.28 μg/ml as compared to protein concentration of control with 6.48 μg/ml. This result indicated the reduction of protein content after the treatment. Protein band pattern was identified intensed after the treatment SDS PAGE was carried out. The thiourea derivatives compound proved to have successfully inhibited the growth of blue-green algae. Hence, further study should be carried out to ensure the compound can be practically utilized in the pond and in natural environment.
This article describes discovery of 29 novel bisindolylmethanes consisting of thiourea moiety, which had been synthesized through three steps. These novel bisindolylmethane derivatives evaluated for their potential inhibitory activity against carbonic anhydrase (CA) II. The results for in vitro assay of carbonic anhydrase II inhibition activity showed that some of the compounds are capable of suppressing the activity of carbonic anhydrase II. Bisindoles having halogen at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. Derivatives showing inhibition activity docked to further, understand the binding behavior of these compounds with carbonic anhydrase II. Docking studies for the active compound 3j showed that nitro substituent at para position fits into the core of the active site. The nitro substituent of compound 3j is capable of interacting with Zn ion. This interaction believed to be the main factor causing inhibition activity to take place.
A high-dimensional quantitative structure-activity relationship (QSAR) classification model typically contains a large number of irrelevant and redundant descriptors. In this paper, a new design of descriptor selection for the QSAR classification model estimation method is proposed by adding a new weight inside L1-norm. The experimental results of classifying the anti-hepatitis C virus activity of thiourea derivatives demonstrate that the proposed descriptor selection method in the QSAR classification model performs effectively and competitively compared with other existing penalized methods in terms of classification performance on both the training and the testing datasets. Moreover, it is noteworthy that the results obtained in terms of stability test and applicability domain provide a robust QSAR classification model. It is evident from the results that the developed QSAR classification model could conceivably be employed for further high-dimensional QSAR classification studies.
Reducing emissions from deforestation and forest degradation-plus (REDD+) is considered as an important mitigation strategy against global warming. However, the implementation of REDD+ can adversely affect local people who have been practicing shifting cultivation for generations. We analyzed Landsat-5 Thematic Mapper images of 1990 and 2009 to quantifying deforestation and forest degradation at Lubuk Antu District, a typical rural area of Sarawak, Malaysia. The results showed significant loss of intact forest at 0.9% per year, which was substantially higher than the rate of Sarawak. There were increases of oil palm and rubber areas but degraded forest, the second largest land cover type, had increased considerably. The local people were mostly shifting cultivators, who indicated readiness of accepting the REDD+ mechanism if they were given compensation. We estimated the monthly willingness to accept (WTA) at RM462, which can be considered as the opportunity cost of foregoing their existing shifting cultivation. The monthly WTA was well correlated with their monthly household expenses. Instead of cash payment, rubber cultivation scheme was the most preferred form of compensation.
A benzoylthiourea molecule namely 1,1-dibenzyl-3-(2-bromobenzoyl)thiourea (2BrBT) was synthesized and characterized
by C, H, N and S elemental, mass spectrometry and spectroscopic analyses (infrared, ultraviolet-visible and nuclear
magnetic resonance). The 2BrBT compound crystallized in a tetragonal system with the space group P43 and exhibits
an acentric crystalline packing due to the presence of intermolecular H-bonding network that forms a self-assembly
of 1D helical motif. The asymmetric delocalisation of electrons in the molecule retains its transparency throughout the
visible and near-infrared region and hence, essentially propagates the macroscopic helical motif in the solid state. The
highest-occupied and lowest-unoccupied molecular orbital (HOMO/LUMO) are mainly found on the thiourea moiety and
the benzoylthiourea fragment, respectively and shows an optical bandgap of 3.50 eV. The influence of its geometrical
characteristics to the optical properties of 2BrBT is established and discussed in view of nonlinear optical (NLO)
application.
Thiourea derivatives display a broad spectrum of applications in chemistry, various industries, medicines and various other fields. Recently, different thiourea derivatives have been synthesized and explored for their anti-microbial properties. In this study, four carbonyl thiourea derivatives were synthesized and characterized, and then further tested for their anti-amoebic properties on two potential pathogenic species of Acanthamoeba, namely A. castellanii (CCAP 1501/2A) and A. polyphaga (CCAP 1501/3A). The results indicate that these newly-synthesized thiourea derivatives are active against both Acanthamoeba species. The IC50 values obtained were in the range of 2.39-8.77 µg·mL⁻¹ (9.47-30.46 µM) for A. castellanii and 3.74-9.30 µg·mL⁻¹ (14.84-31.91 µM) for A. polyphaga. Observations on the amoeba morphology indicated that the compounds caused the reduction of the amoeba size, shortening of their acanthopodia structures, and gave no distinct vacuolar and nuclear structures in the amoeba cells. Meanwhile, fluorescence microscopic observation using acridine orange and propidium iodide (AOPI) staining revealed that the synthesized compounds induced compromised-membrane in the amoeba cells. The results of this study proved that these new carbonyl thiourea derivatives, especially compounds M1 and M2 provide potent cytotoxic properties toward pathogenic Acanthamoeba to suggest that they can be developed as new anti-amoebic agents for the treatment of Acanthamoeba keratitis.
Difatty acyl thiourea (DFAT), which has biological activities as antibiotics and antifungal, has been synthesized from palm oil and thiourea using sodium ethoxide as catalyst. Ethyl fatty ester (EFE) and glycerol were produced as by-products. The synthesis was carried out by reflux palm oil with thiourea in ethanol. In this process, palm oil converted to about 81% pure DFAT after 11 hour and molar ratio of thiourea to palm oil was 6.0: 1 at 78 degrees C. Elemental analysis, Fourier transform iInfrared (FTIR) spectroscopy and (1)H nuclear magnetic resonance (NMR) technique were used to characterize both DFAT and EFE.
In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12)via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC50 value ≤15 µM) in comparison to cisplatin, a positive cytotoxic drug (IC50 value =8.9 ± 1.9 µM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC50 value of 4.7 ± 0.7 µM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of -8.1 kcal/mol as compared to aspirin's binding affinity value of -6.4 kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.
Nanocrystalline lead sulfide (PbS) thin films have been successfully grown on glass substrate using the chemical bath deposition technique. Microwave oven was used as a heating source to facilitate the growth process of the thin films. Aqueous solutions of lead nitrate Pb(NO3) and thiourea [SC(NH2)2] were used as lead and sulfur ion sources, respectively. Structural, morphological and optical analyses revealed good quality growth of nanocrystalline PbS thin films. This study introduced a facile and low cost method to prepare high quality nanocrystalline PbS thin films in a relatively short growth time for optoelectronic applications.
Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
A new isomers of thiourea derivatives, namely N-(4-chlorobutanoyl)-N'-(2-methylphenyl)-thiourea (1a), N-(4-chlorobutanoyl)-N'-(3-methylphenyl)thiourea (1b) and N-(4-chlorobutanoyl)-N'-(4-methylphenyl)thiourea (1c) have been synthesized by refluxing mixture of equimolar amounts of 4-chlorobutanoylisothiocyanate with 2, 3 or 4-toluidine, respectively. The three isomers were characterized by spectroscopic (UV/vis, FT-IR and NMR) and X-ray crystallography techniques. To investigate the isomerization effect on spectroscopic data, DFT and TD-DFT calculations have been carried out using five hybrid functionals (B3LYP, B3P86, CAM-B3LYP, M06-2X and PBE0) to predict UV/vis absorption bands (n→π∗ and π→π∗), (1)H and (13)C NMR chemical shifts, FT-IR vibration modes and X-ray parameters (bonds, bond angles and torsion angles) for 1a, 1b and 1c isomers. The results showed that the isomerization effect is significant on λ(MAX) absorption bands, while for IR and NMR the effect is negligible. In accordance with previous studies, B3LYP, B3P86 and PBE0 gave the most reliable to predict the excitation energies of thiourea derivatives.
A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H &13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h &4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo.
4-Thiazolidinone analogs 1-20 were synthesized, characterized by (1)H NMR and EI-MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC50 values 1.73-69.65μM, if compared with standard thiourea having IC50 value of 21.25±0.15μM. Among the series, eight derivatives 3, 6, 8, 10, 15, 17, 19, and 20 showed outstanding urease inhibitory potential with IC50 values of 9.34±0.02, 14.62±0.03, 8.43±0.01, 7.3±0.04, 2.31±0.002, 5.75±0.003, 8.81±0.005, and 1.73±0.001μM, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies.
Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility. Since clopidogrel, a selective inhibitor of G protein-coupled purinergic P2Y12 receptor (P2Y12R), achieved clinical success as an anti-platelet drug, P2YRs has been attracted more attention as new therapeutic targets of cardiovascular diseases. We have revealed that UDP-responsive P2Y6R promoted angiotensin type 1 receptor (AT1R)-stimulated vascular remodeling in mice, in an age-dependent manner. Moreover, the age-related formation of heterodimer between AT1R and P2Y6R was disrupted by MRS2578, a P2Y6R-selective inhibitor. These findings suggest that P2Y6R is a therapeutic target to prevent age-related hypertension.
Matched MeSH terms: Thiourea/analogs & derivatives; Thiourea/pharmacology; Thiourea/therapeutic use
Proper remediation of aquatic environments contaminated by toxic organic dyes has become a research focus globally for environmental and chemical engineers. This study evaluates the adsorption potential of a polymer-based adsorbent, thiourea-modified poly(acrylonitrile-co-acrylic acid) (T-PAA) adsorbent, for the simultaneous uptake of malachite green (MG) and methylene blue (MB) dye ions from binary system in a continuous flow adsorption column. The influence of inlet dye concentrations, pH, flow rate, and adsorbent bed depth on adsorption process were investigated, and the breakthrough curves obtained experimentally. Results revealed that the sorption capacity of the T-PAA for MG and MB increase at high pH, concentration and bed-depth. Thomas, Bohart-Adams, and Yoon-Nelson models constants were calculated to describe MG and MB adsorption. It was found that the three dynamic models perfectly simulate the adsorption rate and behavior of cationic dyes entrapment. Finally, T-PAA adsorbent demonstrated good cyclic stability. It can be regenerated seven times (or cycles) with no significant loss in adsorption potential. Overall, the excellent sorption capacity and multiple usage make T-PAA polymer an attractive adsorbent materials for treatment of multicomponent dye bearing effluent in a fixed-bed column system.
Disulfide analogs (1-20) have been synthesized, characterized by HR-MS, (1)H NMR and (13)C NMR and screened for urease inhibitory potential. All compounds were found to have varied degree of urease inhibitory potential ranging in between 0.4 ± 0.01 and 18.60 ± 1.24 μM when compared with standard inhibitor thiourea with IC50 19.46 ± 1.20 μM. Structure activity relationship has been established. The binding interactions of compounds with enzyme were confirmed through molecular docking. All the synthesized compounds 1-20 are new. Our compounds are cheaply synthesizable with high yield and can further be studied to discovery lead compounds. We further, tested for carbonic anhydrase, PDE1 and butyrylcholinesterase but they show no activity. On the other hand we evaluated all compounds for cytotoxicity they showed no toxicity.
In this study, simultaneous adsorption of cationic dyes was investigated by using binary component solutions. Thiourea-modified poly(acrylonitrile-co-acrylic acid) (TMPAA) polymer was used as an adsorbent for uptake of cationic dyes (malachite green, MG and methylene blue, MB) from aqueous solution in a binary system. Adsorption tests revealed that TMPAA presented high adsorption of MG and MB at higher pH and higher dye concentrations. It suggested that there are strong electrostatic attractions between the surface functional groups of the adsorbent and cationic dyes. The equilibrium analyses explain that both extended Langmuir and extended models are suitable for the description of adsorption data in the binary system. An antagonistic effect was found, probably due to triangular (MG) and linear (MB) molecular structures that mutually hinder the adsorption of both dyes on TMPAA. Besides, the kinetic studies for sorption of MG and MB dyes onto adsorbent were better represented by a pseudo-second-order model, which demonstrates chemisorption between the polymeric TMPAA adsorbent and dye molecules. According to experimental findings, TMPAA is an attractive adsorbent for treatment of wastewater containing multiple cationic dyes.
An all-solid-state potentiometric electrode system for aluminium ion determination was developed with a new aluminium ion sensor as the working electrode based on a new ionophore for aluminium ion, 1,1'-[(methylazanediyl)bis(ethane-2,1-diyl)]bis[3-(naphthalen-1-yl)thiourea] (ACH). The reference electrode was a potassium ion sensor, which acts as a pseudo-reference. Both electrodes were made from Ag/AgCl screen-print electrodes fabricated from a non-plasticized and photocurable poly(n-butyl acrylate) membrane that contained various other membrane components. The pseudo-reference potential based on the potassium ion sensor was fixed in 0.050 M KNO3, and such concentration of K+ ion did not interfere with the measurement of the Al3+ ion using the aluminium sensor. With such a pseudo-reference and in the presence of 0.050 M KNO3 as a background medium, the aluminium sensor measured changes of aluminium ion concentrations linearly from 10-6 to 10-2 M Al3+ ion with a Nernstian response of 17.70 ± 0.13 mV/decade. A low detection limit of 2.45 × 10-7 M was achieved with this all-solid-state potentiometric system. The aluminium sensor was insensitive to pH effects from 2.0 to 8.0 with a response time of less than 50 s. Under optimum conditions, a lifetime of 49 days was achieved with good sensor selectivity, reversibility, repeatability, and reproducibility. The all-solid-state electrode system was applied to analyze the Al3+ ion content of water samples from a water treatment plant. Compared with the conventional potentiometric detection system for aluminium ions, the new all-solid-state aluminium ion sensor incorporating a pseudo-reference from the potassium sensor demonstrated similar analytical performance. It thus provided a convenient means of aluminium content analysis in water treatment plants.