Autonomous detection of myocarditis based on the fusion of improved quantum genetic algorithm and adaptive differential evolution optimization back propagation neural network.

Myocarditis is cardiac damage caused by a viral infection. Its result often leads to a variety of arrhythmias. However, rapid and reliable identification of myocarditis has a great impact on early diagnosis, expedited treatment, and improved patient survival rates. Therefore, a novel strategy for the autonomous detection of myocarditis is suggested in this work. First, the improved quantum genetic algorithm (IQGA) is proposed to extract the optimal features of ECG beat and heart rate variability (HRV) from raw ECG signals. Second, the backpropagation neural network (BPNN) is optimized using the adaptive differential evolution (ADE) algorithm to classify various ECG signal types with high accuracy. This study examines analogies among five different ECG signal types: normal, abnormal, myocarditis, myocardial infarction (MI), and prior myocardial infarction (PMI). Additionally, the study uses binary and multiclass classification to group myocarditis with other cardiovascular disorders in order to assess how well the algorithm performs in categorization. The experimental results demonstrate that the combination of IQGA and ADE-BPNN can effectively increase the precision and accuracy of myocarditis autonomous diagnosis. In addition, HRV assesses the method's robustness, and the classification tool can detect viruses in myocarditis patients one week before symptoms worsen. The model can be utilized in intensive care units or wearable monitoring devices and has strong performance in the detection of myocarditis.

Synthesis of New Ester Derivatives of Salicylic Acid and Evaluation of Their COX Inhibitory Potential.

Salicylic acid is an NSAID with serious side effects on the GIS. The side effects of salicylic acid on the GIS are slightly reduced by acetylating salicylic acid. 12 new ester analogs of salicylic acid were synthesized with high yields in this study. The chemical structures of the synthesized compounds were characterized by 1 H-NMR, 13 C-NMR, and HRMS spectra. The inhibitory potential of the compounds was evaluated on COXs by in vitro and in silico studies. The COX2 inhibitory activity of the most potent inhibitor MEST1 (IC50 : 0.048 µM) was found to be much higher than the COX2 inhibitory activity of aspirin (IC50 : 2.60 µM). In docking studies, the strongest inhibitor among the compounds synthesized was predicted to be MEST1, with the lowest binding energy. Docking studies revealed that MEST1 extends from the hydrophobic channel to the top of the cyclooxygenase active site, forming various interactions with residues in the binding pocket.

Two-dimensional reciprocal cross entropy multi-threshold combined with improved firefly algorithm for lung parenchyma segmentation of COVID-19 CT image.

The lesions of COVID-19 CT image show various kinds of ground-glass opacity and consolidation, which are distributed in left lung, right lung or both lungs. The lung lobes are uneven and it have similar gray value to the surrounding arteries, veins, and bronchi. The lesions of COVID-19 have different sizes and shapes in different periods. Accurate segmentation of lung parenchyma in CT image is a key step in COVID-19 detection and diagnosis. Aiming at the unideal effect of traditional image segmentation methods on lung parenchyma segmentation in CT images, a lung parenchyma segmentation method based on two-dimensional reciprocal cross entropy multi-threshold combined with improved firefly algorithm is proposed. Firstly, the optimal threshold method is used to realize the initial segmentation of the lung, so that the segmentation threshold can change adaptively according to the detailed information of lung lobes, trachea, bronchi and ground-glass opacity. Then the lung parenchyma is further processed to obtain the lung parenchyma template, and then the defective template is repaired combined with the improved Freeman chain code and Bezier curve. Finally, the lung parenchyma is extracted by multiplying the template with the lung CT image. The accuracy of lung parenchyma segmentation has been improved in the contrast clarity of CT image and the consistency of lung parenchyma regional features, with an average segmentation accuracy rate of 97.4%. The experimental results show that for COVID-19 and suspected cases, the method has an ideal segmentation effect, and it has good accuracy and robustness.

Asymptomatic COVID-19 CT image denoising method based on wavelet transform combined with improved PSO.

The quality of asymptomatic corona virus disease 2019 (COVID-19) computed tomography (CT) image is reduced due to interference from Gaussian noise, which affects the subsequent image processing. Aiming at the problem that asymptomatic COVID-19 CT image often have small flake ground-glass shadow in the early lesions, and the density is low, which is easily confused with noise. A denoising method of wavelet transform with shrinkage factor is proposed. The threshold decreases with the increase of decomposition scale, and it reduces the misjudgment of signal points. In the advanced stage, the range of lesions increases, with consolidation and fibrosis in different sizes, which have similar gray value to the CT images of suspected cases. Aiming at the problems of low contrast and fuzzy boundary in the traditional wavelet transform, the threshold function based on the optimization of parameters combined with the improved particle swam optimization (PSO) is proposed, so that the parameters of wavelet threshold function can change adaptively according to the lung lobe and ground-glass lesions with fewer iterations. The simulation results show that the paper method is significantly better than other algorithms in peak signal-to-noise ratio (PSNR), signal-to-noise ratio (SNR) and mean absolute error (MSE). For example, aiming at the early asymptomatic COVID-19, compared with the comparison methods, the PSNR under the proposed method has increased by about 5 dB, the MSE has been greatly reduced, and the SNR has increased by about 6.1 dB. It can be seen that the denoising effect under the proposed method is the best.

New chalcone derivatives as effective against SARS-CoV-2 agent.

AIMS: Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS-CoV proteases. In this study, we aimed to compare the anti-SARS CoV-2 activities of both newly synthesized chalcone derivatives and these two drugs. METHODS: Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (Ct ) values. RESULTS: Antiviral activities of the compounds varied because of being dose dependent. Compound 6, 7, 9, and 16 were highly effective against SARS-CoV-2 at the concentration of 1.60 µg/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti-coronavirus disease-2019 drug candidates. CONCLUSIONS: Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from -4.370 to -2.748 kcal/mol along with their toxicological, ADME, and drug-like properties.

Novel Mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2(3H)-benzoxazolones.

In this study, a new series of Mannich bases, 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2( 3H )-benzoxazolones ( 1a-g ), were synthesized by the Mannich reaction. Inhibitory effects of the newly synthesized compounds towards carbonic anhydrases (CAs) and acetylcholinesterase (AChE) enzymes were evaluated to find out new potential drug candidate compounds. According to the inhibitory activity results, Ki values of the compounds 1 and 1a-g were in the range of 12.3 ± 1.2 to 154.0 ± 9.3 nM against hCA I, and they were in the range of 8.6 ± 1.9 to 41.0 ± 5.5 nM against hCA II. Ki values of acetazolamide (AZA) that was used as a reference compound were 84.4 ± 8.4 nM towards hCA I and 59.2 ± 4.8 nM towards hCA II. Ki values of the compounds 1 and 1a-g were in the range of 35.2 ± 2.0 to 158.9 ± 33.5 nM towards AChE. Ki value of Tacrine (TAC), the reference compound, was 68.6 ± 3.8 nM towards AChE. Furthermore, docking studies were done with the most potent compounds 1d , 1g , and 1f (in terms of hCA I, hCA II, and AChE inhibition effects, respectively) to determine the binding profiles of the series with these enzymes. Additionally, the prediction of ADME profiles of the compounds pointed out that the newly synthesized compounds had desirable physicochemical properties as lead compounds for further studies.

Synthesis and in silico studies of triazene-substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors.

A novel series of sulfonamides, 4-(3-phenyltriaz-1-en-1-yl)-N-(4-methyl-2-pyrimidinyl)benzenesulfonamides (1-9), was designed and synthesized by the diazo reaction between sulfamerazine and substituted aromatic amines for the first time. Their chemical structures were characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectra. The newly synthesized compounds were evaluated in terms of acetylcholineasterase (AChE) and human carbonic anhydrases (hCA) I and II isoenzymes inhibitory activities. According to the AChE inhibition results, the Ki values of the compounds 1-9 were in the range of 19.9 ± 1.5 to 96.5 ± 20.7 nM against AChE. Tacrine was used as the reference drug and its Ki value was 49.2 ± 2.7 nM against AChE. The Ki values of the compounds 1-9 were in the range of 10.2 ± 2.6 to 101.4 ± 27.8 nM against hCA I, whereas they were 18.3 ± 4.4 to 48.1 ± 4.5 nM against hCA II. Acetazolamide was used as a reference drug and its Ki values were 72.2 ± 5.4 and 52.2 ± 5.7 nM against hCA I and hCA II, respectively. The most active compounds, 1 (nonsubstituted) against AChE, 5 (4-ethoxy-substituted) against hCA I, and 8 (4-bromo-substituted) against hCA II, were chosen and docked at the binding sites of these enzymes to explain the inhibitory activities of the series. The newly synthesized compounds presented satisfactory pharmacokinetic properties via the estimation of ADME properties.

Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors.

N -(1-(4-Methoxyphenyl)-3-oxo-3-((4-( N -(substituted)sulfamoyl)phenyl)amino)prop-1-en-1-yl)benzamides 3a - g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and hCA II) inhibitory potencies. Structure elucidation of the compounds was carried out by 1H NMR, 13C NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 ± 0.38 - 29.70 ± 3.18 nM for hCA I and 10.68 ± 0.98 - 37.16 ± 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 ± 1.65 - 34.02 ± 5.90 nM. The most potent inhibitors 3g (Ki = 4.07 ± 0.38 nM, hCA I), 3c (Ki = 10.68 ± 0.98 nM, hCA II ) , and 3f (Ki = 8.91 ± 1.65 nM, AChE) can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes.

Novel sulphonamides incorporating triazene moieties show powerful carbonic anhydrase I and II inhibitory properties.

A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I and II. KI values of these sulphonamides were in the range of 21 ± 4-72 ± 2 nM towards hCA I and in the range of 16 ± 6-40 ± 2 nM against hCA II. The 4-fluoro substituted derivative might be considered as an interesting lead due to its effective inhibitory action against both hCA I and hCA II (KIs of 21 nM), a profile rarely seen among other sulphonamide CA inhibitors, making it of interest in systems where the activity of the two cytosolic isoforms is dysregulated.

Synthesis of novel bis-sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase.

In this study, a series of novel bis-sulfone compounds (2a-2j) were synthesized by oxidation of the bis-sulfides under mild reaction conditions. The bis-sulfone derivatives were characterized by 1 H-NMR, 13 C-NMR, Fourier-transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis-sulfone derivatives. Here, we report the synthesis and testing of novel bis-sulfone compound-based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward the therapy of Alzheimer's disease. The novel synthesized bis-sulfone compounds demonstrated Ki values between 11.4 ± 3.4 and 70.7 ± 23.2 nM on human carbonic anhydrase I isozyme (hCA I), 28.7 ± 6.6 to 77.6 ± 5.6 nM on human carbonic anhydrase II isozyme (hCA II), 18.7 ± 2.61 to 95.4 ± 25.52 nM on AChE, and 9.5 ± 2.1 to 95.5 ± 1.2 nM on BChE enzymes. The results showed that novel bis-sulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.

Synthesis and Cytotoxicities of New Azafluorenones with Apoptotic Mechanism of Action and Cell Cycle Analysis.

BACKGROUND: In this study, new azafluorenones, 4-(4-fluorophenyl)-2-(4-substitutedphenyl)-5Hindeno[ 1,2-b] pyridin-5-one, I1-I8 were synthesized and chemical structures were elucidated by spectral analysis. All compounds were reported for the first time here. METHOD: Compounds were tested in terms of cytotoxicity. They were found as cytotoxins/anticancer compounds. RESULTS: It was found that the lead compounds of the series were I5 and I8 according to SI, TS, PSE calculations. When PSE values were considered, compound I5 having chlorine had the highest PSE value of 126.4. Second highest PSE value of 50.5 belonged to I8, which had thiophene ring in its chemical structure. I8 as a representative compound of the series was forwarded to cell cycle analysis. I8 arrested S phase of the cell cycle and lead to apoptosis by inducing PARP cleavage suggesting that at least one of the mechanisms of cytotoxic action of the series was apoptosis. CONCLUSION: It was clearly demonstrated that compound I8 can induce early apoptosis at a concentration of 5 µM. The compounds I5 and I8 can be considered as lead compounds of the series with the highest SI, TS, PSE values for further studies.

Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents.

The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aß1-42) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer's disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1-22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman's colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of Aß1-42 aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09 µM. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of Aß1-42 aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD.

Synthesis of donepezil-based multifunctional agents for the treatment of Alzheimer's disease.

Amyloid beta (Aß) and cholinesterase enzymes (AChE, BuChE) are important biological targets for the effective treatment of Alzheimer's disease. In this study, the aim was to synthesize new donepezil-like secondary amide compounds that display a potent inhibition of cholinesterases and Aß with antioxidant and metal chelation abilities. All test compounds showed activities against both ChEs and ß1-42 inhibition. The most encouraging compound, 20, is an AChE inhibitor with high anti-aggregation activity (55.3%). Based on the results, compound 20 may be a promising structure in further research for new anti-Alzheimer's agents.

Microwave-assisted synthesis, molecular docking, and cholinesterase inhibitory activities of new ethanediamide and 2-butenediamide analogues.

A novel series of meta-substituted ethanediamide and 2-butenediamide derivatives were synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (AChE) and equine serum butyrylcholinesterase (BuChE). The synthesized compounds were evaluated against ChE enzymes using the colorimetric method described by Ellman et al. (Biochem. Pharmacol., 7, 1961). It was revealed that some synthesized compounds exhibited high anticholinesterase activity, among which compounds 1f and 2f were the most active inhibitors against BuChE (IC50 value=1.47 µM) and AChE (IC50 value=2.09 µM), respectively. Docking simulations revealed that the inhibitors 1f and 2f are capable of simultaneously binding the peripheral anionic site as well as the catalytic anionic site of both ChE enzymes. These derivatives are considered interesting candidates for Alzheimer's disease treatment.

Preparation, anticholinesterase activity, and docking study of new 2-butenediamide and oxalamide derivatives.

Several new oxalamide and 2-butenediamide derivatives have been designed, synthesized and evaluated as the acetyl- and butyryl-cholinesterase inhibitors for Alzheimer's disease. The enzyme inhibitory activity of the synthesized compounds was measured using Ellman's colorimetric method. It was revealed that compound 1a (N,N'-bis-(4-chloro-benzyl)-N,N'-diphenyl-oxalamide) showed maximum activity against BuChE with a half maximal inhibitory concentration (IC50) = 1.86 µM and compound 2a (but-2-enedioic acid bis-[(4-chloro-benzyl)-phenyl-amide]) exhibited optimum AChE (IC50 = 1.51 µM) inhibition with a high-selectivity index. To better understand the enzyme-inhibitor interaction of the most active compounds towards cholinesterase, molecular modelling studies were carried out. Docking simulations revealed that inhibitors 1a and 2a targeted both the catalytic active site and the peripheral anionic site of 1ACJ and 1P0I.