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In this study, Centaurea sivasica Wageitz (Asteraceae) methanol extract was examined regarding phytochemical composition, in vitro antioxidant properties, ability to inhibit tyrosinase, α-amylase, α-glucosidase enzymes, and antimicrobial effects. Also, possible binding and interactions of phytochemicals with enzymes by molecular docking were determined. The extract's phenolic amount was 21.42 mg GAE/g extract, and the extract was determined to be rich in flavonoids (19.73 mg RE/g extract). Due to the results of liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) analysis, the main components of the methanol extract was scutellarin (27843.91 μg/g), quercimeritrin (3629.85 μg/g), chlorogenic acid (2519.68 μg/g) and baicalin (920.49 μg/g). The methanol extract was found to show remarkable activity in all antioxidant activity tests and had a high potential to inhibit the enzymes examined. The extract was radical scavenging on (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum assays were measured as 2.72, 69.58, 44.78, 141.18, 109.25 mg TE/g extract, respectively. Tyrosinase, α-amylase, and α-glucosidase inhibitory activities were 36.81 mg KE/g extract, 252.60 and 279.40 mg AKE/g extract, respectively. Scutellarin inhibited the tyrosinase enzyme very effectively, and its effect was found as 43.32 µM or 20.38 µg/mL. The extract showed different inhibition zones (16.3, 16.0, 15.0, 15.6 mm) and MIC values (500–1000 µg/mL) on the microorganisms examined (B. cereus, S. aureus, E. coli, C. albicans). In molecular docking studies, the most abundant scutellarin in the extract was shown to affect both tyrosinase and α-glucosidase inhibition significantly.

New Schiff bases were synthesized (Z)-4-((4-(diethylamino) benzylidene) amino)-N-(3,4-dimethylisoxazol-5-yl) benzenesulfonamide (L1) and (Z)-4-((4-(dimethylamino)benzylidene)amino)-N-(5-methylisoxazol-3-yl) benzenesulfonamide (L2) derived from sulfamethoxazole (S1)/sulfisoxazole (S2) and substituted salicylaldehyde. The synthesized compounds were characterized by FT-IR, H-1-C-13 NMR, LC-MS. We evaluated the effects of compounds on eight enzyme activities by spectrophotometric assays at final concentrations of 0.5-5 mu g. L1 acted as an inhibitor on cholesterol esterase, tyrosinase and alpha-amylase activities with IC50 values 38, 38 and 173 mu M. Tyrosinase, alpha-glucosidase, cholesterol esterase, and a-amylase enzymes were inhibited by L2 with IC50 values 24, 46, 63, and 231 mu M. To comprehend the binding interactions between the inhibitors and enzymes with low IC50 values, molecular docking studies of compounds were performed for cholesterol esterase and tyrosinase. Finally, molecular docking was performed to determine the probable binding mode of the designed compounds into the active site of enzymes. DFT calculations were carried out at the B3LYP levels of theory with 6-311G ++ (d, p) basis set for compounds. (C) 2019 Elsevier B.V. All rights reserved.

The fluorinated chalcones were synthesized by Claisen-Schmidt condensation between 4′-morpholineacetophenone and various fluorinated benzaldehydes in the presence of NaOH in methanol. The synthesized compounds [1–7] were evaluated their antiproliferative activity against HeLa and C6 cell lines. Among them, compounds 4 and 5 were determined to have anticancer activity against HeLa cells line (IC 50 values of 7.74 and 6.10 μg/mL, respectively). The anticancer activity results were shown that compounds 3 , and 6 had inhibitory against C6 cells (IC 50 values of 12.80 and 4.16 μg/mL, respectively). The compounds 1 and 2 had high antiproliferative activity with non-cytotoxicity. All of the new compounds, except for compound 4 showed inhibition against the human isozyme hCA I with IC 50 in the range of 0.5–1,16 mM. Pyruvate kinase M2 (PKM2) was effectively inhibited by compound 4 with IC 50 = 26 μM.

Background : SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. Purpose : This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. Methods : A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. Results : Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. Conclusion : This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models., Graphical Abstract Image, graphical abstract

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called “Iskin” by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, β-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the NαFmoc- l -Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with NαFmoc- l -Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the NαFmoc- l -Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from −7.30 and −10.62 kcal/mol.