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Objective: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium. Methods: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and β-secretase. Results: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of β-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with β-secretase in docking studies. Binding energies for interaction of β-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing β-secretase expression in the Alzheimer's disease model. [ABSTRACT FROM AUTHOR]

Bidentate Schiff bases (I1–I9) are synthesized by condensation between substituted anilines, benzothiazoles, and 2-hydroxy aromatic aldehydes. The Zn(II) derivatives (1–9) are prepared by reacting the respective ligand and zinc acetate dihydrate in a 2:1 mole ratio in dry methanol using triethylamine as a base. They are characterized by FTIR, NMR, and single-crystal XRD techniques. The XRD data confirmed distorted tetrahedral molecular geometry for 6; the intermolecular interactions are investigated comprehensively by 3-D Hirschfeld surface analysis and 2-D fingerprint plots. The DFT studies for the compounds are conducted for geometrical and energy optimization by applying 3-21 G* and 6-311++G (d, p)/B3LYP basis sets. Molecular docking data show that ligands possess GOLD scores in the range 51.5–46.7, whereas 2 and 3 have shown good fitness score of 57.7 and 53.3, respectively, with a maximum score of 60.2 for 7. The antibacterial data for 7 shows zone of inhibition as 17.3 mm against Staphylococcus aureus and 16.3 mm against Staphylococcus epidermidis, whereas 2 exhibits maximum value of 15.6 mm against gram negative bacteria Escherichia coli. The maximum and comparable alpha amylase inhibition potential of 12.6 and 12.3% are found for 8 and 3, respectively. [ABSTRACT FROM AUTHOR]

A series of 18 biologically active C5‐arylated‐2‐isobutylthiazole derivatives that were synthesized by Pd‐NHC complexes [Pd(μ‐Cl)Cl (NHC)]2, NHC = SIXyl, 2), (LCl2Pd‐NHC, L = PPh3, 3), (LCl2Pd‐NHC, L = Py, 4), (LCl2Pd‐NHC, L = 3‐CHO‐Py, 5) catalyzed C‐H bond activation reactions. The catalytic activity of Pd‐NHC complexes was examined on the C‐H bond activation reaction of 2‐isobutylthiazole. All Pd‐NHC complexes were characterized by 1H nuclear magnetic resonance specroscopy (NMR), 13C NMR, fouirer transform infrared spektroscopy (FTIR), quadrupole‐time of flying‐liquit cromotagraphy/mass spektroscopy (Q‐TOF‐LC/MS), gas chromatography–mass spectrometry (GCMS), and melting point detection technique. The physicochemical properties, pharmacokinetics, and drug‐likeness were calculated by SwissADME. PkCSM database was used to calculate toxicities profile. All the products (6a–6s) were additionally assessed in vitro for their antidiabetic potential using α‐amylase and α‐glucosidase inhibitory activities. The protein kinase activity was performed to evaluate their anticancer activities. All the compounds possess drug‐like characters as they followed Lipinski's rule of five (RO5). Almost all the compounds showed no to fewer toxicities. In addition, other than the compounds, that is, 6a, 6b, 6c, 6m, 6n, 6p, and 6s, the rest of the compounds showed good α‐glucosidase inhibitory potential (IC50 7.17 ± 0.201 to 74.08 ± 0.244 μg/ml) when compared with acarbose standard (IC50 16.59 ± 0.135 μg/ml). All compounds had moderate to good inhibitory potential against the α‐amylase enzyme, with IC50 values ranging from 12.00 ± 0.289 to 76.15 ± 0.477 μg/ml. Eleven analogs (6e, 6f, 6g, 6h, 6j, 6k, 6l, 6n, 6o, 6p, and 6r) showed good to moderate activity. Seven analogs (6a, 6b, 6c, 6d, 6i, 6m, and 6s) showed no α‐amylase inhibitory activity. The protein kinase inhibition potential was determined for the first time, and the compounds 6d, 6e, 6f, 6h, 6k, 6p, and 6r depicted activity with the zone of inhibition in the range of 9 ± 1.3 to 19 ± 1.5 mm. The ligands and active site binding interactions of α‐glucosidase, α‐amylase, and protein kinase enzymes were also studied using molecular modeling. [ABSTRACT FROM AUTHOR]

In a quest to discover new formulations for the treatment of various parasitic diseases, a series of heteroleptic triorganobismuth(V) biscarboxylates of type [BiR3(O2CR′)2], where R=C6H5 for 1–4 and p-CH3C6H4 for 5–8, were synthesized, characterized and evaluated for their biological potential against L. tropica. All the synthesized complexes were fully characterized by elemental analysis, FT-IR, multinuclear (1H and 13C) NMR spectroscopy and X-ray crystallography. The crystal structures for [BiPh3(O2CC6H4(o-Br))2] (1), [BiPh3(O2CC2H2C6H4)2] (2), [BiPh3(O2CC6H4(m-NO2))2] (3) and [BiPh3(O2CC6H4(2-OH,3-CH3))2] (4) were determined and found to have a distorted pentagonal bipyramidal molecular geometry with seven coordinated bismuth center for 1–3 and for 4 distorted octahedral geometry, respectively. All the synthesized complexes demonstrated a moderate to significant activity against leishmania parasites. A broad analytical approach was followed to testify the stability for (1–8) in solid state as well as in solution and in leishmanial culture M199, ensuring them to be stable enough to exert a significant antileishmanial effect with promising results. Cytotoxicity profile suggests that tris(tolyl) derivatives show lower toxicity against isolated lymphocytes with higher antileishmanial potential. Molecular docking studies were carried out to reveal the binding modes for (1–8) targeting the active site of trypanothione reductase (TR) (PDB ID: 4APN) and Trypanothione Synthetase-Amidase structure (PDB ID 2vob). [ABSTRACT FROM AUTHOR]

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica. The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani. Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (Kd, −9.4 and −8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections. [ABSTRACT FROM AUTHOR]

Abstract In current research, five series of mono- and di-substituted piperazine derivatives have been synthesized. For di-substituted derivatives, ciprofloxacin was selected and hybrids were synthesized via substitution at piperazinyl- N 4 . In vitro antibacterial studies of all synthesized compound were carried out against American Type Culture Collection (ATCC) strains; E. coli (ATCC 25922), P. aeruginosa (ATCC 15442), K. pneumoniae (ATCC 1705), B. subtilis (ATCC 6633) and S. aureus (ATCC 6538). The potent series of compounds were further evaluated for their potential against clinically isolated resistant strains of E. coli , P. aeruginosa , S. aureus , and S. hemolytic. The reaction of piperazinyl-NH of ciprofloxacin with selected drugs resulted in pronounced growth inhibition of standard as well as resistant bacterial strains. Hybrid compounds 14b , 16a , 16d and CGS-20 showed excellent bacterial growth inhibition against standard and resistant strains. In vitro results were further correlated by using in silico tools. Molecular docking studies were carried out using MOE (Molecular Operating Environment) software. DNA gyrase used as a target and all compounds were docked against this specific target. Graphical abstract Image 1 Highlights • Mono- and di-substituted piperazine derivatives were synthesized. • In di-substituted derivatives, ciprofloxacin-drug hybrids were synthesized. • Compounds were evaluated against normal and resistant bacterial strains. • Excellent in vitro bacterial strain inhibition by some compounds. • Molecular docking studies on DNA gyrase as target. [ABSTRACT FROM AUTHOR]

• Pd(II)-NHC complexes used as catalysts in direct C H arylation reaction of caffeine. • The C8-(hetero)aryl xanthines were obtained in good to excellent yields. • Different C8-(hetero)aryl xanthines which are important to biological applications were synthesised for the first time. • Molecular docking, antioxidant, antifungal, antibacterial and enzyme inhibitory evaluations of 8-(hetero)aryl xanthines were examined. A series of 8-(hetero)aryl caffeine was synthesized by the C H bond activation reaction using Pd-NHCs complexes as a catalyst. 8-(hetero)aryl caffeine derivatives were screened for their antioxidant, antimicrobial, and enzyme inhibitory activities and in-silico studies. The 4a, 4b, 4e, 4f, 4 g, 4i, and 4n showed significant total antioxidant capacity (TAC) of 64.03, 50.87, 70.02, 98.14, 71.81, 45.48, and 44.28 µg AAE/mg, respectively. The 4a, 4b, 4d, 4e, 6 h, 4i, 4j, 4k, and 4l were found active against Staphylococcus aureus at a minimum inhibitory concentration of 25, 12.5, 12.5, 12.5, 12.5, 6.25, 6.25, 6.25, and 6.25 µg/ml, respectively. Some derivatives displayed activity against Escherichia coli, Bacillus subtilus, Klebsiella pneumonae, and Pseudomonas aeruginosa. A good activity was exhibited against Alternaria solani among five fungal strains. All the compounds (4a–4n) showed excellent protein kinase inhibitory activity except 4e, 4 g, and 4n. Additionally, 8-(hetero)aryl caffeine derivatives showed α-amylase inhibition potential (IC50 = 1.49 ± 0.317 to 7.44 ± 0.156 μg/ml) compared to standard acarbose (IC50 = 4.34 ± 0.333 μg/ml). The 4b, 4d, 4j, 4 m, and 4n compounds displayed good α-glucosidase inhibitory potential. Molecular modeling was done for protein kinase, α-amylase, and α-glucosidase. The results of these activities proved the caffeine derivatives to be bioactive. [Display omitted] [ABSTRACT FROM AUTHOR]

• · Eight new bioactive bismuth(III) hydrazones were synthesized and fully characterized, besides the solvent molecule, DMSO, contribute to their structural motifs. • X-ray structure for 1 revealed a distinctive seven coordinated Bi(III) center, assuming pentagonal bipyramidal molecular geometry. • · The compounds 6, 7 and 8 exhibited significant antidiabetic activity. • · Molecular docking study revealed significant activity of 2 against Human pancreatic alpha amylase with the highest GOLD fitness score. • · The docking data for (1) described its active role against H. pylori urease having the highest GOLD fitness score. Eight new bismuth(III) complexes (1-8) of substituted hydrazones having general formula; [Bi(RCONHNCHC 5 H 4 N)Cl x ] and [Bi(RCONHNCHC 9 H 6 N)Cl x ], where R = C 10 H 7 O (1, and 8) , C 4 H 3 S (2) , C 6 H 5 O (3, and 6), C 7 H 7 (4), C 5 H 4 N (5, and 7), x = 2 or 3 have been prepared. The substituted hydrazones (I 1 -I 8) were synthesized by reacting the stoichiometric amounts of the respective hydrazides such as p-toluic hydrazide, 4-hydroxybenzhydrazide, thiophene-2-carboxylic acid hydrazide, 3-hydroxy-2-naphthoic acid hydrazide, Isonicotic acid hydrazide and appropriate aromatic aldehydes like pridine-2-carboxaldehyde and quinoline-2-carboxyaldehyde. These hydrazones (ligands),then complexed to Bi(III) species to yield the target compounds. They were characterized by FTIR, and NMR spectroscopy to find out an explicit evidence about their structural motifs. The X-ray data for (1 & I 6) further validate the chemical structures of the synthesized compounds. The molecular geometry for (1) is predominately distorted pentagonal bipyramidal where hepta-coordinated Bi(III) center is attached to the nitrogens of pyridine and of azomethine moieties along with the carbonyl oxygen, two chloro and two oxygens of the (two) DMSO molecules. The bond lengths for Bi(1)-O(1), Bi(1)-N(1) and Bi(1)-N(2) are 2.323(5), 2.539(6), 2.390(5) oA respectively indicating Bi(1)-O(1) as the strongest linkage to the metal center. The H-bonding, present in (1), contributed an extra stability to the structure. The synthesized compounds were initially screened for their possible antimicrobial, alpha-amylase, and protein kinase inhibition, some (1,2,6,8) exhibit significant activity. The experimental results are further endorsed by molecular docking studies against helicobacter pylori urease (1E9Y), epidermal growth factor receptor tyrosine kinase (1M17) and human pancreatic alpha amylase (5U3A) inhibition activity. The significant ligand-receptor interactions, observed at the binding pocket of the selected drug targets, further revealed the enzyme inhibition potential of the compounds and highlighting their possible roles as therapeutic agents in future drug discovery processes. [ABSTRACT FROM AUTHOR]