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Thiazolidinedione (TZD) based medications have demonstrated to enhance the insulin sensitivity control, hyperglycemia, and lipid metabolism in patients with type 2 diabetes. Hence, in this study, a new series of novel coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones (TZD1-TZD18) were synthesized via copper (I)-catalyzed azide-alkyne cycloaddition "Click Chemistry". The synthesized compounds were evaluated for their glucose uptake assay and in vitro cytotoxicity against HEK-293 (human embryonic kidney) cells which were compared with the standard drug Pioglitazone. Further, molecular docking analysis of these compounds was carried out to explain the in vitro results with PPARγ (PDB ID: 3CS8) and to better understand the bonding interactions with the target protein. The outcomes of in vitro assessment, molecular docking, and pharmacokinetics of the title compounds were revealed to be highly correlated. Interestingly, the compounds TZD4, TZD10, TZD14 and TZD16 were most efficient in lowering the blood glucose level compared with standard drug.

β-Secretase (BACE1) has been broadly documented as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synthesis of tetrahydrobenzo [b] pyrans was carried out by condensing aromatic aldehyde, malononitrile and 1,3-cyclohexanedione using ionic liquid 1-butyl-3-methyl imidazolium chloride ([bmIm]Cl-) in aqueous alcohol media. The addition of alcohol and water in the ratio of 1:2 keeps all the reactants in solution which facilitates the reaction and makes the product formation very easy. The synthesized compounds were subjected to BACE1 inhibition assay and six compounds, 4d, 4e, 4f, 4h, 4i, and 4p have shown significant IC50 values at micromolar level. Among these six active compounds, 4e was a potential inhibitor with its IC50 value in nanomolar range. All the synthesized compounds were docked onto the active site of β-Secretase enzyme.

In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis H37Rv as well as inhibitors of InhA. Among them, few representative compounds were tested for mammalian cell toxicity on the human lung cancer cell-line (A549) and MV cell line that presented no cytotoxicity. Five of these compounds exhibited a good activity against InhA.

Background A hybrid molecule of different biologically active substances can improve affinity and efficiency compared to a standard drug. Hence based on this fact, we predict that a combination of fluorine, oxadiazole, sulfur, etc., may enhance α-glucosidase inhibition activity compared to a standard drug. Methods A series of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives (2a-2i) were synthesized and characterized using spectroscopic techniques such as 1HNMR and LC-MS. In order to evaluate its bioactivity, in vitro α-amylase and α-glycosidase inhibitory activity were performed. In vivo study was carried using a genetic model, Drosophila melanogaster, for assessing the antihyperglycemic effects. Results The compounds 2a-2i demonstrated α-amylase inhibitory activity in the range of IC50 = 40.00–80.00 μg/ml as compare to standard acarbose (IC50 = 34.71 μg/ml). Compounds 2a-2i demonstrated α-glucosidase inhibitory activity in the range of IC50 = 46.01–81.65 μg/ml as compared to standard acarbose (IC50 = 34.72 μg/ml). Docking studies on a target protein, N-terminal subunit of human Maltase-glucoamylase (PDB:2QMJ) was carried and the compounds were found to dock into the active site of the enzyme (Fig. 1). The predicted binding energies of the compounds were calculated. The in vitro studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. Whereas in vivo study indicates that 2b, 2g, and 2i could lower glucose levels in the Drosophila, but then 17–30% reduced capacity than acarbose and may be overcome by adjusting their dosage. Conclusions The in vitro and in vivo studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. This study has recognized that compounds like 2b, 2g, and 2i may be considered potential candidates for further developing a novel class of antidiabetic agents.

An efficient, high yields and rapid synthesis of N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide derivatives (4a–4j) under microwave-irradiation has been described. All the newly synthesized compounds (4a–4j) were characterized by elemental analysis and spectroscopic studies. The synthesised compounds (4a–4j) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compound (4f) exhibits antibacterial effect with MIC–2.5 μg/mL against gram positive S. aureus bacterial strain compared to standard ciprofloxacin drug (MIC–10 μg/mL). The compound (4c) shows an inhibition of heat induced protein denaturation 75.42% at a concentration of 31.25 μg/ml and is almost ten times more active than compared to standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising.

A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction. Furthermore, all compounds were evaluated for antimicrobial activity against five bacteria and two fungi. Last but not the least, molecular docking studies with Candida albicans dihydropteroate synthetase were performed and the results are presented herein.

Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript.

Enoyl acyl carrier protein reductase (ENR)is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents.Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA).Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods.