Thyroid cancer has been increasingly prevalent in recent years. The main diagnostic methods for thyroid are B-ultrasound scan, serum detection and puncture detection. However, these methods are ...invasive and complex. It is a pressing need to develop non-invasive or minimally invasive methods for thyroid cancer diagnosis. Fluorescence method as a non-invasive detection method has attracted much attention. Butyrylcholinesterase (BChE) is a common enzyme in the human body, and many diseases affect its reduction. We found that BChE is also a marker for thyroid cancer. Therefore, it is of certain clinical value to explore the expression of BChE in thyroid cancer cells through a customized fluorescent probe to provide valuable experimental data and clues for studying the expression of thyroid cancer marker to reflect thyroid status.
In this study, we customized a fluorescent probe named Kang-BChE, which is easy to synthesize with a high yield. The experimental results show that the probe Kang-BChE can detect BChE in the linear range of 0–900 U L−1 (R2 = 0.9963), and the detection limit is as low as 3.93 U L−1 (λex/em = 550/689 nm). In addition, Kang-BChE probes have low cytotoxicity, good specificity, and can completely eliminate interference from acetylcholinesterase (AChE). Kang-BChE showed excellent stability in the detection of complex biological samples in serum recovery experiments (95.64–103.12 %). This study was the first time using Kang-BChE to study the low expression of BChE in thyroid cancer cells (Tpc-1 cells). In addition, we observed that H2O2 concentration in Tpc-1 cells was positively correlated with BChE activity.
Kang-BChE is expected to be an important tool for monitoring the change of BChE content in complex biological environments due to its excellent performance. Kang-BChE can also be used to explore the influence of molecules in more organisms on the change of BChE content due to its excellent anti-interference ability. We expect that Kang-BChE can play a significant role in the clinical diagnosis and treatment of thyroid cancer.
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•Kang-BChE was first to observe the change of BChE content in Tpc-1 cells.•Kang-BChE can completely eliminate the interference of AChE.•Kang-BChE has good stability in complex biological samples.•Kang-BChE observed positive correlation between H2O2 and BChE in Tpc-1 cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Synthesis of mono and disubstituted 4-amino benzohydrazides.•Evaluating the 4-amino benzohydrazide derivative compounds as a potential acetylcholinesterase and butyrylcholinesterase ...inhibitors.•Molecular docking analyze of 4-amino benzohydrazide derivative compounds in active site of acetylcholinesterase and butyrylcholinesterase.
Nowadays, inhibition of the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes have emerged as an encouraging approach in the treatment of dementia and remission of symptoms of Alzheimer's disease. Therefore, inhibition of cholinesterases is one of the main targets by researchers. Benzohydrazides are biologically active compounds and have various pharmacological effects, bearing these in mind, we investigated the inhibitory effects of some mono or di-substituted 4-aminobenzohydrazide derivatives (1a-11a) against AChE and BChE. For this purpose, we studied the inhibition effects (IC50, Ki values, and inhibition types) of these molecules on AChE and BChE enzymes. Based on the results, compound 3a showed potent AChE and BChE inhibition (IC50 = 0.59 and 0.15 μM). The Ki values of the compounds (3a, 4a, and 8a) showing the best inhibition effect against AChE and BChE were calculated and these values ranged from 0.10 ± 0.04 to 5.10 ± 2.14 μM. To determine the possible binding mechanisms with the active sites of both enzymes of compounds 3a, 4a, and 8a having strong inhibitory effects, docking analyses were performed. According to the docking results, compound 3a showed the best binding affinity (-7.3 kcal/mol for AChE and -6.8 kcal/mol for BChE) against both enzymes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Novel cholinesterase inhibitors were designed and synthesized based on Clopidogrel bisulfate.•TA2 bearing methoxy substituent has the highest antioxidant activity in the series.•TA11 bearing bromo ...substituent showed approximately 5-fold higher inhibitory activity against both AChE and BChE compared to Donepezil.•Kinetic studies revealed that TA11 was a competitive inhibitor.
Due to the lack of an effective treatment for Alzheimer's disease, there is a need for the development of new and effective compounds. The synthesis of some new hydrazone derivatives (TA1-TA14) based on Clopidogrel bisulfate has been carried out. IR, 1H NMR, 13C NMR, 2D-NMR (HSQC) and MS spectroscopic techniques were used to elucidate the chemical structures of the compounds. Antioxidant and cholinesterase activities of the compounds were evaluated. Compound TA2 bearing bromo substituent has the highest antioxidant activity in the series. Compound TA11 bearing methoxy substituent exhibited the highest inhibitory activity in the series with IC50 values of 8.540 ± 0.015 µM and 7.980 ± 0.026 μM against AChE and BChE, respectively. Kinetic studies (Lineweaver-Burk plots) revealed that TA11 was a competitive inhibitor. In addition, molecular docking studies aimed to elucidate the interactions between these designed compounds and key enzymes, including AChE and BChE. TA11 has been evaluated as a promising candidate for further studies to develop new agents in the fight against Alzheimer's disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Organophosphorus (OP) pesticides have been used widely as agricultural and household pest control agents for almost five decades and persist in our water resources, fruits, vegetables and processed ...food as health and environmental hazardous compounds. Thus, detection of these harmful OP pesticides at an ease with high sensitivity and selectivity is the need of hour. Bio-sensing technology meet these requirements and has been employed at a large scale for detection. The present review is aimed mainly to provide the overview of the past and recent advances occurred in the field of biosensor technology employed for the detection of these OP compounds. The review describes the principle and strategy of various OP biosensors including electrochemical (amperometric, potentiometric), thermal, piezoelectric, optical (fluorescence, Surface Plasmon Resonance (SPR)), microbial and DNA biosensors in detail. The electrochemical biosensors are generally, based on inhibition of enzyme, acetyl cholinesterase (AChE), butyryl cholinesterase (BChE), tyrosinase and alkaline phosphatase or enzyme (organophosphorus hydrolase, OPH)) catalyzed reaction. The detection limits and linearity range of various OP biosensors have also been compared. AChE inhibition based amperometric OP biosensors exhibited the lowest detection limit of 1 × 10−11 μM with a linearity range of 1.0 × 10−11 – 1.0 × 10−2 μM.
Scheme: Overview of bio-sensing techniques employed for the detection of organophosphorus (OP) compounds. Display omitted
•OP pesticides determination has great relevance in environmental monitoring and sustainable agriculture.•At large, various enzymes, AChE, BChE, tyrosinase, alkaline phosphatase inhibition based and OPH hydrolysis based biosensors has been fabricated so far.•AChE inhibition based amperometric OP biosensors have the lowest detection limit of 1 × 10−11 μM and linearity range of 1.0 × 10−11 – 1.0 × 10−2 μM among all the biosensors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Agriculture production has been supported especially by the use of pesticides for crop protection and pest control. Although the agricultural production has been increased by pesticides use, these ...substances also reach non-target organisms and may become a risk to the health of farmers. Several epidemiological studies in human have investigated the association between exposure to pesticides and altered serum levels of thyroid hormones, reporting both positive and negative results. Overall, the impact of pesticides on human thyroid function is still limited.
The aim of this study was to access serum levels of free thyroxin (FT4), total triiodothyronine (TT3), thyroid-stimulating hormone (TSH), and butyrylcholinesterase (BChE) in soybean farmers in southern Brazil.
The exposed group was composed by 46 rural workers and 27 subjects not exposed to pesticides composed the control group. All subjects had blood samples collected by venipuncture in order to analyze the serum levels of FT4, TT3, TSH and BChE.
The results showed a significant decreasing in TSH and increasing in TT3 and FT4 in rural workers, compared to control group. BChE levels were lower in exposed group than in control group. The results suggest that farmers are exposed to mixtures of pesticides with endocrine disruptor properties.
•Soybean farmers and control group were studied for pesticide exposure effects.•BChE and thyroid hormones were evaluated.•BChE levels were lower in the exposed group.•TSH was increased and TT3 and FT4 decreased in soybean farmers.•Soybean farmers are exposed to BChE inhibitors and thyroid-disrupting pesticides.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Butyrylcholinesterase (BChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD), the development of selective BChE inhibitors has attracted a great deal of interest and may be ...a viable therapeutic strategy for AD. Previously, an aromatic tertiary amine derivative (S17–1001) was screened and validated as a selective BChE inhibitor. Structured-based molecular modification guided the synthesis of 43 analogs. Biological test of cholinesterase inhibition, in vitro blood brain barrier permeation assay, neurotoxicity assay and neuroprotective effects assay indicated two optimal compounds 17c and 19c. Both compounds showed selective BChE inhibitory (hBChE < 20 nM, eeAChE > 10 μM), good BBB permeation and primary cell safety. Besides, 17c can dose-response protect cell from Aβ1−42 induced damage. It also demonstrated that 17c and 19c were able to restore cognitive impairment in vivo test. These data suggest that 17c and 19c represent promising candidate for follow-up in the drug-discovery process against AD.
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•Novel aromatic tertiary amine derivatives were determined as selective butyrylcholinesterase inhibitors.•Not trigger acute toxicity on mice and obvious neurotoxicity on cells.•Significantly reversed Aβ-induced memory deficit in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Molecular docking is a powerful and significant approach for the identification of lead molecules on the basis of virtual screening. With it a large number of compounds can be tested and based on the ...scoring function and ranking, the conclusion can be made about how the selected compounds can inhibit the targeted protein/receptor. Considering the importance of selective inhibitors of cholinesterase in the treatment of Alzheimer disease, this research is focused on the determination of the mechanism of binding interactions of few benzene-1,3-diol derivatives within the active site of both acetyl-cholinesterase (AChE) and butyrylcholinesterase (BChE). All the selective ligands were found to have a greater binding affinity with the BChE when compared to that of AChE, by an average value of ~?28.4 and ~?12.5 kJ/mol, respectively. The results suggested that the identified inhibitors can be used as the lead compounds for the development of novel inhibitors of the targeted enzymes against some specific diseases, thus opening the possibility of new therapeutic strategies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Industrial and human activities contribute significantly to the environmental contamination of heavy metal ions (HMIs), which have detrimental effects on aquatic life, plants, and animals, causing ...major toxicological problems. The commercially available 4,4′-diamino-2,2′-stilbenedisulfonic acid (DSD) has been playing a vital role in the detection of heavy metal ions and has significantly inhibited a variety of cancer cells in numerous field of modern science. The current investigation aimed to ensure the detection of heavy metals ions from the environment and fluorescence imaging of DSD in the treatment of cancer cells. Fluorescence and UV-Visible spectroscopic analysis was performed to sense the selective behavior of the probe DSD with several heavy metal ions, including Fe2+, K1+, Co2+, Ni2+, Zn2+, Cd2+, Pb2+, Mn2+, Sn2+, and Cr3+. Furthermore, DSD was subjected to examine enzyme inhibition such as anti-Alzheimer, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities in search of multifaceted drugs. Test compounds have demonstrated dose-dependent responses in the in-vitro enzyme inhibition assays for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), cyclooxygenase (COX), and lipoxygenase (LOX), as well as antioxidant DPPH = 2,2-diphenyl-1-picrylhydrazyl and ABTS = 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid. The DSD were shown to be more effective than the conventional medication galantamine in inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with an IC50 value of 12.18 and 20.87 μM, which is equivalent to the standard drug. The results obtained has revealed that DSD has the potential to become an effective sensor for the detection of Sn2+ ions over competing metal ions due to the inhibition of photo-induced electron transfer pathway (PET). The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide tetrazolium) test, demonstrated that DSD had strong anticancer effects against the brain cancer cell line NIH/3T3, HeLa and MCF-7 with an IC50 value of 32.59, 15.31 and 96.46 μM respectively. The antimicrobial testing has shown that DSD outperforms the standard drug cefixime against Candida albicans and Pseudomonas aeruginosa, respectively. This study makes a substantial contribution to the ongoing search for efficient treatments for breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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