Functional,antioxidant and antibacterial properties of protein hydrolysates prepared from fish meat fermented by Bacillus subtilis A26

Composition, functional properties and in vitro antioxidant and antibacterial activities of protein hydrolysates prepared with a proteolytic bacterium, Bacillus subtilis A26, through fermentation of fish proteins were investigated. Fermented fish meat protein hydrolysates (FPHs) were prepared from sardinelle (SPH), zebra blenny (ZPH) goby (GPH) and ray (RPH). The protein content of freeze-dried FPHs ranged from 74.3% to 81%. All fermented hydrolysates had an excellent solubility and possessed interfacial properties. The antioxidant activities of FPHs were evaluated by different methods, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method, reducing power assay, β-carotene bleaching and DNA nicking assay. All hydrolysates showed dose-dependent antioxidant activities. Further, FPHs exhibited antibacterial activity and SPH was the most effective, particularly against Gram positive bacteria.     

Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory,antioxidant and antimicrobial agents

A novel series of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (3) have been prepared by the Claisen–Schmidt condensation of 1-(2,4-dimethoxy-phenyl)-ethanone (1) and substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (2). Substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (2) were prepared by Vilsmeir–Haack reaction on acetophenonephenylhydrazones to offer the target compounds. The structures of the compounds were established by IR, ¹H NMR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory (TNF-α and IL-6 inhibitory assays), antioxidant (DPPH free radical scavenging assay) and antimicrobial activities (agar diffusion method) against some pathogenic bacteria and fungi. Of 10 compounds screened, compounds 3a, 3c and 3g exhibited promising IL-6 inhibitory (35–70% inhibition, 10 μM), free radical scavenging (25–35% DPPH activity) and antimicrobial activities (MIC 100 μg/mL and 250 μg/mL) at varied concentrations. The structure–activity relationship (SAR) and in silico drug relevant properties (HBD, HBA, PSA, c Log P, molecular weight, E_HOMO and E_LUMO) further confirmed that the compounds are potential lead compounds for future drug discovery study. Toxicity of the compounds was evaluated theoretically and experimentally and revealed to be nontoxic except 3d and 3j.     

Organochalcogen compounds from glycerol: Synthesis of new antioxidants

We describe here a simple method for the synthesis of glycerol derivatives containing an organochalcogen unit (Se, Te and S) using NaBH₄ and PEG-400 as a solvent. The new methodology was used to synthesize a range of new organochalcogen compounds in good yields. Furthermore, four of synthesized compounds were evaluated for their antioxidant activity using different assays, such as 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, nitric oxide (NO) and hydroxyl radical (OH) scavenging, ferric ion reducing antioxidant power (FRAP), ferrous ion chelating, superoxide dismutase-like activity and inhibition of linoleic acid lipid peroxidation. The new organotellurium 2,2-dimethyl-4-(phenyltellanylmethyl)-1,3-dioxolane 3j showed antioxidant activity and was more effective in inhibition of induced lipid peroxidation compared to solketal 4. Selenium and sulfur analogs 3a and 3m and solketal 4 did not present antioxidant effect. These findings suggest that 2,2-dimethyl-4-(phenyltellanylmethyl)-1,3-dioxolane 3j is a promising antioxidant and that its activity is influenced by the presence of the tellurium atom on the structure.     

Fungal metabolites of xanthohumol with potent antiproliferative activity on human cancer cell lines in vitro

Xanthohumol (1) and xanthohumol D (2) were isolated from spent hops. Isoxanthohumol (3) was obtained from xanthohumol by isomerisation in alkaline solution. Six metabolites were obtained as a result of transformation of xanthohumol (1) by selected fungal cultures. Their structures were established on the basis of their spectral data. One of them: 2″-(2′′′-hydroxyisopropyl)-dihydrofurano-[4″,5″:3′,4′]-4′,2-dihydroxy-6′-methoxy-α,β-dihydrochalcone (6) has not been previously reported in the literature. The antioxidant properties of hops flavonoids and xanthohumol derivatives were investigated using the 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The effects of these compounds on proliferation of MCF-7, PC-3 and HT-29 human cancer cell lines were determined by the SRB assay. With the exception of one metabolite, all tested compounds showed antiproliferative activity against the tested human cancer lines. α,β-Dihydroxanthohumol (4), obtained through the biotransformation of xanthohumol, showed higher antiproliferative activity against MCF-7 human breast carcinoma cell line than cisplatin, a widely used anticancer therapeutic agent, and a comparably high activity against PC-3 human prostate cancer cell line.     

Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant,acetylcholinesterase, butyrylcholinesterase,and tyrosinase inhibitory profile

Abstract

A series of 16 novel benzenesulfonamides incorporating 1,3,5-triazine moieties substituted with aromatic amines, dimethylamine, morpholine and piperidine were investigated. These compounds were assayed for antioxidant properties by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical decolarisation assay and metal chelating methods. They were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase, which are associated with several diseases such as Alzheimer, Parkinson and pigmentation disorders. These benzenesulfonamides showed moderate DPPH radical scavenging and metal chelating activity, and low ABTS cation radical scavenging activity. Compounds 2?b, 3d and 3?h showed inhibitory potency against AChE with % inhibition values of >90. BChE was also effectively inhibited by most of the synthesised compounds with >90% inhibition potency. Tyrosinase was less inhibited by these compounds.     

Exploration of antimicrobial and antioxidant potential of newly synthesized 2,3-disubstituted quinazoline-4(3H)-ones

A series of 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones 9a-j was synthesized by treating 2-(chloroacetyl)amino benzoic acid with 3-amino-6-methyl-5-[(E)-phenyldiazenyl]-2-thioxo-2,5-dihydropyrimidine-4(3H)-one 8a-j and was screened for in vitro antibacterial activities against a representative panel of Gram-positive and Gram-negative bacteria. The compounds were synthesized in excellent yields and the structures were corroborated on the basis of IR, ¹H NMR, Mass and elemental analysis data. All the synthesized compounds elicited the potent inhibitory action against all the tested bacterial stains. Furthermore, in order to explore the antioxidant potential of newly synthesized compounds, the free radical scavenging activity measurement were performed by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay method. It is revealed from the antioxidant screening results that the compounds 9c and f manifested profound antioxidant potential.     

Design,synthesis, evaluation,and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents

Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100?mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen. The cytotoxicity of the compounds was also assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC₅₀ >100?μmol/L). Furthermore, molecular docking studies of the synthesized compounds were performed to rationalize the obtained biological results. Overall, the results indicate that compound 11b could be a therapeutic candidate for the treatment of inflammation.     

Chemical components and its antioxidant properties in vitro: An edible marine brown alga,Ecklonia cava

Seven phlorotannins were isolated and characterized from an edible marine brown alga Ecklonia cava (EC), along with three common sterol derivatives (fucosterol, ergosterol, and cholesterol) according to the comprehensive spectral analysis of MS and NMR data. Compounds 5 (7-phloro eckol) and 7 (6,6′-bieckoll) of phlorotannin derivatives were obtained for the first time with the high yields. No reports of compound 3 (Fucodiphloroethol G) was published up to date. The antioxidant properties of all phlorotannins were assessed by total antioxidant activity in a linoleic acid model, free radicals scavenging assay using electron spin resonance spectrometry (ESR) technique, cellular reactive oxygen species (ROS) assay by DCFH-DA, membrane protein oxidation assay; measurement of cellular glutathione (GSH) level in RAW264.7 cell line, and myeloperoxidase (MPO) assay in HL-60 cell line. The results revealed that all phlorotannins had antioxidant properties in vitro, especially, compounds 7 (6,6′-bieckol), 6, and 3 showed the significant activities compared to the other phlorotannins. Furthermore, the structure–activity relationship (SAR) was discussed based on the structural differences of the tested phlorotannins which have polymeriged phloroglucinal units with diverse skeletons and linkages. It could be suggested that phlorotaninns from this genus would be more potential candidates for the development of unique natural antioxidants for further industrial applications as functional foods, cosmetics and pharmaceuticals. As well as our results makes it clear to understand the reason behind the use of EC as traditional folk herb for a long history.     

Catechol thioethers with physiologically active fragments: Electrochemistry,antioxidant and cryoprotective activities

A number of asymmetrical thioethers based on 3,5-di-tert-butylcatechol containing sulfur atom bonding with physiologically active groups in the sixth position of aromatic ring have been synthesized and the electrochemical properties, antioxidant, cryoprotective activities of new thioethers have been evaluated. Cyclic voltammetry was used to estimate the oxidation potentials of thioethers in acetonitrile. The electrooxidation of compounds at the first stage leads to the formation of o-benzoquinones. The antioxidant activities of the compounds were determined using 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) assay, experiments on the oxidative damage of the DNA, the reaction of 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) induced glutathione depletion (GSH), the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro, and iron(II) chelation test. Compounds 1–9 have greater antioxidant effectiveness than 3,5-di-tert-butylcatechol (CatH₂) in all assays. The variation of physiologically active groups at sulfur atom allows to regulate lipophilic properties and antioxidant activity of compounds. Thioethers 3, 4 and 7 demonstrate the combination of radical scavenging, antioxidant activity and iron(II) binding properties. The researched compounds 1–9 were studied as possible cryoprotectants of the media for cryopreservation of the Russian sturgeon sperm. Novel cryoprotective additives in cryomedium reduce significantly the content of membrane-permeating agent (DMSO). A cryoprotective effect of an addition of the catechol thioethers depends on the structure of groups at sulfur atom. The cryoprotective properties of compounds 3, 4 and 7 are caused by combination of catechol fragment, bonded by a thioether linker with a long hydrocarbon chain and a terminal ionizable group or with a biologically relevant acetylcysteine residue.     

Synthesis and in vitro evaluation of vanillin derivatives as multi-target therapeutics for the treatment of Alzheimer’s disease

A number of novel naphthalimido and phthalimido vanillin derivatives were synthesised, and evaluated as antioxidants and cholinesterase inhibitors in vitro. Antioxidant activity was assessed using DPPH, FRAP, and ORAC assays. All compounds demonstrated enhanced activity compared to the parent compound, vanillin. They also exhibited BuChE selectivity in Ellman’s assay. A lead compound, 2a (2-(3-(bis(4-hydroxy-3-methoxybenzyl)amino)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione), was identified and displayed strong antioxidant activity (IC₅₀ of 16.67 µM in the DPPH assay, a 25-fold increase in activity compared to vanillin in the FRAP assay, and 9.43 TE in the ORAC assay). Furthermore, 2a exhibited potent BuChE selectivity, with an IC₅₀ of 0.27 µM which was around 53-fold greater than the corresponding AChE inhibitory activity. Molecular modelling studies showed that molecules with bulkier groups, as in 2a, exhibited better BuChE selectivity. This work provides a promising basis for the development of multi-target hybrid compounds based on vanillin as potential AD therapeutics.     

Design,synthesis and anti-Alzheimer properties of dimethylaminomethyl-substituted curcumin derivatives

Eight dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized. The antioxidant test revealed that the synthesized compounds had higher free radical scavenging activity towards both 2,2-diphenyl-1-picrylhydrazyl free radicals (DPPH) (IC₅₀ 1.5–29.9 μM) and galvinoxyl radicals (IC₅₀ 4.9–41.1 μM) than the lead compound curcumin. Besides, compound 3a could effectively inhibit the Aβ self-aggregation in vitro. Investigated in phosphate-buffered solutions (pH = 7.4) in the presence or absence of 0.1% FBS 3a showed a good stability while curcumin did not. Furthermore, 3a showed a good lipophilicity (log P = 3.48), suggesting a potential ability to penetrate the blood–brain-barrier. The aqueous solubility of the hydrochloride salt of 3a (16.7 mg/mL) has also been significantly improved as compared with curcumin (<0.1 mg/mL).     

Synthesis,antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

A series of 2-arylbenzimidazole derivatives (3a–3p and 4a–4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O₂^?) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC₅₀ = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H₂O₂-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.     

Synthesis of pyrazole encompassing 2-pyridone derivatives as antibacterial agents

A series of novel compounds 6-amino-1-((1,3-diphenyl-1H-pyrazole-4-yl)methyleneamino)-4-(aryl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles (4a–t) were synthesized and characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. These compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes (Gram positive), Escherichia coli, Pseudomonas aeruginosa (Gram negative) by serial broth dilution and cytotoxic activity (NIH 3T3 & HeLa) by MTT assay. The results indicated that compounds 4g, 4i, 4m, 4o, 4r and 4t exhibit potent antibacterial activity against bacterial strains at non-cytotoxic concentrations.     

Two tetrahydroisoquinoline alkaloids from the fruit of Averrhoa carambola

The fruit of Averrhoa carambola, commonly known as star fruit or carambola, is popular in Southeast Asia and China. Two new tetrahydroisoquinoline alkaloids, (1R*,3S*)-1-(5-hydroxymethylfuran-2-yl)-3-carboxy-6-hydroxy-8-methoxyl-1,2,3,4-tetrahydroisoquinoline (1) and (1S*,3S*)-1-methyl-3-carboxy-6-hydroxy-8-methyoxyl-1,2,3,4-tetrahydroisoquinoline (2), were isolated from the fruit, along with vanillic acid (3), ferulic acid (4), 8,9,10-trihydroxythymol (5), and arjunolic acid (6). Their structures were elucidated by spectroscopic method. Compounds 1, 2, and 5 showed weak ferric reducing antioxidant potency (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity.     

Conventional and microwave assisted synthesis of pyrazolone Mannich bases possessing anti-inflammatory,analgesic, ulcerogenic effect and antimicrobial properties

In the present study, an efficient synthesis of some Mannich base of 5-methyl-2-[(2-oxo-2H-chromen-3-yl)carbonyl]-2,4-dihydro-3H-pyrazol-3-one (4a–j) have been described by using conventional and non-conventional (microwave) techniques. Microwave assisted reactions showed that require shorter reaction time and good yield. The newly synthesized compounds were screened for their anti-inflammatory, analgesic activity, antioxidant, and antibacterial effects were compared with standard drug. Among the compounds studied, compound (4f) showing nearly equipotent anti-inflammatory and analgesic activity than the standard drug (indomethacin), along with minimum ulcerogenic index. Compounds (4b and 4i) showing 1.06 times more active than ciprofloxacin against tested Gram-negative bacteria.     

Synthesis,tautomerism, and antimicrobial,anti-HCV,anti-SSPE,antioxidant, and antitumor activities of arylazobenzosuberones

2-Dimethylaminomethylene-1-benzosuberone 1 was coupled with diazotized aniline derivatives to afford a series of the hitherto unreported 2-arylazo-1-benzosuberones 3a–i. The tautomeric structure and the effect of substituents on the tautomeric form (s) of the products 3a–i were discussed. Similar coupling of the enaminone 1 with diazonium salts of heterocyclic amines gave the respective fused azolotriazino-benzosuberones. Some of the newly synthesized compounds showed potent antimicrobial, anti-HCV, antioxidant, antitumor (as topoisomerase I inhibitors), and antimicrobial activities.     

Two new antioxidant flavones from the twigs of Eriosema robustum (Fabaceae)

Phytochemical study of the ethanol extract of the twigs of Eriosema robustum, a Cameroonian medicinal plant resulted to the isolation of two new flavones, 2′,3′,5′,5,7-pentahydroxy-3,4′-dimethoxyflavone (1) and 2′,3,5′,5,7-pentahydroxy-4′-methoxyflavone (2), along with five known compounds: 6-prenylpinocembrin (3), 1-O-heptatriacontanoyl glycerol (4), β-sitosterol (5), stigmasterol (6) and 3-O-β-d-glucopyranoside of sitosterol (7). The structure of the isolated compounds were elucidated on the basis of their NMR, UV and MS data, and by comparison with those reported in the literature. The ethanol crude extract, fractions and some isolated compounds (1–4) were evaluated for their radical scavenging capacity using 2,2-diphenyl-1-picryhydrazyl (DPPH). The crude extract, fraction II, the new compounds namely robusflavones A (1) and B (2) exhibited significant antioxidant activity.     

Synthesis,pharmacological screening and in silico studies of new class of Diclofenac analogues as a promising anti-inflammatory agents

A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1,3,4-oxadiazol-2(3H)-thione (4a–k) derivatives have been synthesized by the Mannich reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)-thione (3) with an appropriately substituted primary/secondary amines, in the presence of formaldehyde and absolute ethanol. Structures of these novel compounds were characterized on the basis of physicochemical, spectral and elemental analysis. The title compounds (4a–k) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 10 mg/kg b.w. Compound 4k exhibited the most promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e, 4i, and 4j showed moderate to good inhibitory activity at 2nd and 4th h, respectively. These compounds were also found to have considerable analgesic activity (acetic acid induced writhing model) and antipyretic activity (yeast induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. Compounds that displayed promising anti-inflammatory profile were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition against COX-2. In an attempt to understand the ligand–protein interactions in terms of the binding affinity, docking studies were performed using Molegro Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti-inflammatory activity. It was observed that the binding affinities calculated were in agreement with the IC₅₀ values.     

Total phenolics, flavonoids and antioxidant activity of Saptarangi (Salacia chinensis L.) fruit pulp

Salacia chinensis L. has various beneficial properties including antidiabetic and antioxidant activity. The S. chinensis fruit pulp (SCFP) was extracted with four different solvents (Methanol, ethanol, acetone and water) and was screened for total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity (AOA). The AOA was assessed by evaluating the 1, 1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and metal chelating assay. Methanolic SCFP extract exhibited the highest phenolic content (3.20?±?0.12 mg GAE/g FW) whereas, ethanolic extract showed highest flavonoid content (0.31?±?0.68 mg RE/g FW). The methanolic extract possesses highest antioxidant activity towards DPPH (92.44 %), FRAP (1.939 O.D) and metal chelating activity (74.16 %). AOA (DPPH and FRAP) was significantly correlated with TPC. The results indicated that SCFP is a good natural source of antioxidant compounds for use in food and pharmaceutical industry.     

Antioxidant activity of benzoxazolinonic and benzothiazolinonic derivatives in the LDL oxidation model

A series of benzazolone compounds were synthesized utilizing benzoxazolinonic and benzothiazolinonic heterocycles as the building unit. The antioxidant activity of these compounds was determined by inhibition of lipid peroxidation. The oxidation of LDL was induced in the presence of CuSO₄ or 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). The protective action of these compounds against the cytotoxicity was evaluated with lactate dehydrogenase (LDH) activity in bovine aortic endothelial cells (BAECs) and cellular vitality by measuring mitochondrial activity in the presence of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The best antioxidant activities were observed for phenolic compounds 13 and 14b with ratio R = 2.5, 3.2 (5 μM). Both of these test substances increased the cell viability significantly as indicated by MTT assay and LDH release assay.