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New pyridothieno[3,2-b]indole and pyridothieno[3,2-c]cinnoline derivatives are designed and prepared from the corresponding 3-amino-2-arylthieno[2,3-b]pyridines. By a molecular docking method novel potential inhibitors of DNA gyrase B are identified among the thieno[2,3-b]pyridine derivatives. In addition, some of the prepared pyridothienoindoles exhibit in vivo antidote activity against the herbicide 2,4-D.

Test means based on immobilized Fehling’s reagent for the determination of cephalexin have been obtained. Methods for visual and colorimetric assessment of antibiotic concentration using a smartphone camera have been developed. The optimal conditions for the indicator reaction have been selected with varying heating time and temperature. For a visual semi-quantitative assessment of the content of cephalexin, a color scale has been obtained. The metrological characteristics of the test method have been determined: the range of the determined contents is 0.5–16 mg/ml, the unreliability interval is 0.1–0.4 mg/ml, and the detection limit is 0.4 mg / ml. For the colorimetric assessment of the concentration of cephalexin, a linear dependence of the intensity of the Blue channel on the logarithm of the concentration of cephalexin (у = –96x + 144, r 2 = 0.99) has been constructed, and linear dependences of the area (у = –36986x + 62458, r 2 = 0.96) and perimeter (у = –270x + 786, r 2 = 0.93) from the logarithm of the concentration of cephalexin have been obtained. The range of the determined contents was 0.1–16 mg/ml, the lower limit was 0.1 mg / ml. The verification of the correctness of the developed test methods was carried out by the «introduced-found» method (Sr  0.13).

A simple and fast method for determination of cephalexin using test papers with immobilized Fehling's reagent is reported. Color scales for the naked-eye determination of cephalexin were constructed. Based on RGB-analysis linear correlations between the intensities of the blue and green color channels, the concentration of cephalexin were obtained. Furthermore, the possibility of using radar charts for the analyte was investigated. For detection of antibiotic, the authors��� application for smartphone ��Digital colorimetric test�� was created. After loading a photo of the paper-based device, the application automatically displays the concentration of antibiotic on the screen. Moreover, for detection of the antibiotic, a small volume of sample (5 ��L) is required. The limits of detection for developed methods were from 0.13 to 0.4 mg/mL (Sr < 0.12).

The main (Mpro) and papain-like (PLpro) proteases are highly conserved viral proteins essential for replication of the COVID-19 virus, SARS-COV-2. Therefore, a logical plan for producing new drugs against this pathogen is to discover inhibitors of these enzymes. Accordingly, the goal of the present work was to devise a computational approach to design, characterize, and select compounds predicted to be potent dual inhibitors - effective against both Mpro and PLpro. The first step employed LigDream, an artificial neural network, to create a virtual ligand library. Ligands with computed ADMET profiles indicating drug-like properties and low mammalian toxicity were selected for further study. Initial docking of these ligands into the active sites of Mpro and PLpro was done with GOLD, and the highest-scoring ligands were redocked with AutoDock Vina to determine binding free energies (ΔG). Compounds 89-00, 89-07, 89-32, and 89-38 exhibited favorable ΔG values for Mpro (-7.6 to -8.7 kcal/mol) and PLpro (-9.1 to -9.7 kcal/mol). Global docking of selected compounds with the Mpro dimer identified prospective allosteric inhibitors 89-00, 89-27, and 89-40 (ΔG -8.2 to -8.9 kcal/mol). Molecular dynamics simulations performed on Mpro and PLpro active site complexes with the four top-scoring ligands from Vina demonstrated that the most stable complexes were formed with compounds 89-32 and 89-38. Overall, the present computational strategy generated new compounds with predicted drug-like characteristics, low mammalian toxicity, and high inhibitory potencies against both target proteases to form stable complexes. Further preclinical studies will be required to validate the in silico findings before the lead compounds could be considered for clinical trials.

Background: Antibiotic resistance, which occurs through the action of metallo-β-lactamases (NDM-1), is a serious problem in the treatment of infectious diseases. Therefore, the discovery of new NDM-1 inhibitors and promising antibacterial agents as inhibitors of alternative targets (MetAP-1) is important. Method & results: In this study, a virtual library of 5-arylidene barbituric acids was created and molecular docking was performed for identification of novel possible inhibitors of NDM-1 and MetAP-1. Antibacterial activity (agar well-diffusion assay) and cytotoxicity (alamarBlue assay) of perspective compounds were evaluated. Pharmacokinetic profiles and molecular properties were predicted. Conclusion: We have identified possible novel inhibitors of NDM-1 and MetAP-1 with bacteriostatic activity, most of which are not cytotoxic and have potential excellent drug-likeness properties.

Graphical abstract, The main protease (3CLpro) of SARS-CoV and SARS-CoV-2 is a promising target for discovery of novel antiviral agents. In this paper, new possible inhibitors of 3CLpro with high predicted binding affinity were detected through multistep computer-aided molecular design and bioisosteric replacements. For discovery of prospective 3CLpro binders several virtual ligand libraries were created and combined docking was performed. Moreover, the molecular dynamics simulation was applied for evaluation of protein-ligand complexes stability. Besides, important molecular properties and ADMET pharmacokinetic profiles of possible 3CLpro inhibitors were assessed by in silico prediction.