Elicitation with abiotic stresses improves pro-health constituents,antioxidant potential and nutritional quality of lentil sprouts

Phenolic content and antioxidant potential of lentil sprouts may be enhanced by treatment of seedlings in abiotic stress conditions without any negative influence on nutritional quality.The health-relevant and nutritional quality of sprouts was improved by elicitation of 2-day-old sprouts with oxidative, osmotic, ion-osmotic and temperature stresses. Among the sprouts studied, those obtained by elicitation with osmotic (600 mM mannitol) and ion-osmotic (300 mM NaCl) shocks had the highest total phenolic content levels: 6.52 and 6.56 mg/g flour, respectively. Oxidative stress significantly enhanced the levels of (+)-catechin and p-coumaric acid. A marked elevation of the chlorogenic and gallic acid contents was also determined for sprouts induced at 4 °C and 40 °C. The elevated phenolic content was translated into the antioxidant potential of sprouts, especially the ability to reduce lipid oxidation. A marked elevation of this ability was determined for seedlings treated with 20 mM, 200 mM H₂O₂ (oxidative stress) and 600 mM mannitol (osmotic stress); about a 12-fold, 8-fold and 9.5-fold increase in respect to control sprouts. The highest ability to quench free radicals was observed in sprouts induced by osmotic stress (IC₅₀- 4.91 and 5.12 mg/ml for 200 mM and 600 mM mannitol, respectively). The highest total antioxidant activity indexes were determined for sprouts elicited with 20 mM H₂O₂ and 600 mM mannitol: 4.0 and 3.4, respectively. All studied growth conditions, except induction at 40 °C, caused a significant elevation of resistant starch levels which was also affected in a subsequent reduction of starch digestibility.Improvement of sprout quality by elicitation with abiotic stresses is a cheap and easy biotechnology and it seems to be an alternative to conventional techniques applied to improve the health promoting phytochemical levels and bioactivity of low-processed food.     

Gold(III) compounds as anticancer agents: relevance of gold-protein interactions for their mechanism of action

Gold(III) compounds constitute an emerging class of biologically active substances, of special interest as potential anticancer agents. During the past decade a number of structurally diverse gold(III) complexes were reported to be acceptably stable under physiological-like conditions and to manifest very promising cytotoxic effects against selected human tumour cell lines, making them good candidates as anti-tumour drugs. Some representative examples will be described in detail. There is considerable interest in understanding the precise biochemical mechanisms of these novel cytotoxic agents. Based on experimental evidence collected so far we hypothesize that these metallodrugs, at variance with classical platinum(II) drugs, produce in most cases their growth inhibition effects through a variety of "DNA-independent" mechanisms. Notably, strong inhibition of the selenoenzyme thioredoxin reductase and associated disregulation of mitochondrial functions were clearly documented in some selected cases, thus providing a solid biochemical basis for the pronounced proapoptotic effects. These observations led us to investigate in detail the reactions of gold(III) compounds with a few model proteins in order to gain molecular-level information on the possible interaction modes with possible protein targets. Valuable insight on the formation and the nature of gold-protein adducts was gained through ESI MS (electrospray ionization mass spectrometry) and spectrophotometric studies of appropriate model systems as it is exemplified here by the reactions of two representative gold(III) compounds with cytochrome c and ubiquitin. The mechanistic relevance of gold(III)-induced oxidative protein damage and of direct gold coordination to protein sidechains is specifically assessed. Perspectives for the future of this topics are briefly outlined.     

Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents

A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models.     

Biologically and chemically important hydrazino-containing imidazolines as antioxidant agents

Biologically and chemically useful hydrazinoimidazolines were evaluated as antioxidant and antihaemolytic agents. 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH^?), galvinoxyl radical (GOR), nitric oxide (NO) and hydrogen peroxide (H₂O₂) scavenging assays, ferric ions reducing power assay, and ex vivo model of rat erythrocytes exposed to 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AAPH) or H₂O₂ were used. The most potent DPPH^? scavengers proved to be hydrazinoimidazolines 3, 2, and 4, revealing excellent antiradical effects – superior or comparable to that of all antioxidant standards used. Moreover, these molecules showed strong NO neutralising potencies – better to that of ascorbic acid (AA) (3), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) (3 and 2), butylated hydroxytoluene (BHT) (3 and 2), and butylated hydroxyanisole (BHA) (3, 2, and 4). Compound 4 was also effective in GOR scavenging. The excellent scavenger of GOR, NO, and H₂O₂ proved to be structure 5, with the potency superior or comparable to the majority of antioxidant standards used. In turn, compound 9 was effective in H₂O₂ and GOR neutralisation. All hydrazinoimidazolines revealed the reducing power that is higher than BHT. Moreover, the protective effects of most test compounds on oxidatively stressed erythrocytes were observed. Some structure–activity relationships were disclosed. A significance of the primary hydrazino group on antioxidant effects was confirmed. The most likely DPPH^? and GOR scavenging mechanisms for test compounds were propound. Among all the investigated molecules, hydrazinoimidazolines 5, 3, 2, 4, and 9, due to their excellent or good antiradical activities, can represent promising antioxidant candidates with prospective utility for prevention of diseases related to reactive oxygen/nitrogen species.     

Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant,photoprotective and antiproliferative activity of indole hydrazones

Two series of indole derivatives 4–17, 20–22 were easily prepared and assayed for their radical-scavenging ability. Arylidene-1H-indole-2-carbohydrazones showed different extent antioxidant activity in DPPH, FRAP and ORAC assays. Good antioxidant activity is related to the number and position of hydroxyl groups on the arylidene moiety as well as to the presence of methoxy or 4-(diethylamino) group. On the contrary low antioxidant activity is showed by the isomeric 1H-indol-2-yl(methylene)-benzohydrazides. Furthermore, hydrazones 4–17 showed photoprotective capacities with satisfactory in vitro SPF as compared to the commercial PBSA sunscreen filter. The indole 16 and 17, showing the best antioxidant and photoprotective profile, were included in different formulation and their topical release was evaluated. Varying the formulation composition, it was possible to optimize skin adsorption and solubility of the active indole in the formulation. The antiproliferative effect of the hydrazones 4–17 was tested on human erythroleukemia K562 and melanoma Colo-38 cells. Hydrazones 11, 16 and 17 showed growth inhibition at sub micromolar concentrations on both cell lines. These results indicate indole hydrazones as potential multifunctional molecules especially in the treatment of neoplastic diseases being the good antioxidant properties of 16 and 17 correlated to their high antiproliferative activity.     

Desert legume Prosopis cineraria as a novel source of antioxidant flavonoids / isoflavonoids: Biochemical characterization of edible pods for potential functional food development

Flavonoids and isoflavonoids in foods are attracting attention as they are significant antioxidant and phytoestrogenic compounds that are beneficial for human health. In this study, the edible pods of the underutilized desert legume Prosopis cineraria from Rajasthan, India were used to extract flavonoids. The pods from semi-arid zone showed the highest flavonoid content (432 mg Rutin hydrate/gm). UV spectrophotometric analysis was also done to characterize flavonoids. The flavonoids and isoflavonoids were further purified from semi-arid zone plants using column chromatography with Amberlite XAD7HP and Sephadex LH-20. LC-MS analysis revealed the presence of medicinally valuable antioxidant flavonoids and isoflavonoids in the pods, viz. vitexin, puerarin, phloridzin, and daidzein. It was seen that the flavonoids/isoflavonoids are present in the selected legume in different forms i.e. pure aglycone, C-glycoside as well as O-glycoside. This finding makes P. cineraria an attractive source candidate for extraction of these nutraceuticals with a potential for development into functional food.     

中药抗卵巢癌作用及机制研究新进展

卵巢癌是女性常见的生殖器官恶性肿瘤之一,严重威胁着女性的生殖健康.中药治疗卵巢癌具有多靶点、多途径、毒副作用小等特点,近年来已成为国内外学者的研究热点.本文系统总结了中药复方药、植物药(多糖、黄酮类、生物碱、酚类、萜类、醌类、皂苷、酯类、挥发油、醚类)、动物药及矿物药抗卵巢癌的活性及作用机制,并初步分析了中药有效成分抗...     

South African Lippia herbal infusions: Total phenolic content,antioxidant and antibacterial activities

Lippia javanica and Lippia scaberrima are used as herbal remedies and are commercially traded as health teas in southern Africa under the brands “Mosukujane” and “Musukudu”, respectively. This study evaluates the relationship between the presence of phenolic compounds and the antioxidant activities of infusions prepared from four Lippia species (L. javanica, L. scaberrima, L. rehmannii and L. wilmsii) indigenous to South Africa. The antioxidant activities of the infusions, determined by the 2,2-diphenylpycrylhydrazyl (DPPH) method, were also compared to those of popular black, green and herbal tea brands. Of the four indigenous species, infusions of L. javanica and L. wilmsii exhibited the highest antioxidant activities (EC₅₀: 358 and 525 µg/ml, respectively) and contained the most phenolic compounds (14.8 and 14.5 mg/ml of dry weight gallic acid equivalent, respectively). Antibacterial activities of methanolic extracts of the four Lippia species were determined against four human pathogens (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa). The extract of L. javanica was the most active against all the pathogens tested. Those Lippia species (L. javanica and L. wilmsii) previously reported to produce higher levels of the pharmacologically active phenylethanoid glycosides verbascoside and isoverbascoside, portrayed stronger antioxidant and antibacterial activities. This study gives credence to the use of infusions of these Lippia species for their general health benefits.     

Synthesis and characterization of trans-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanes as ligands for the melanocortin-4 receptor

A series of trans-N-alkyl-4-(4-chlorophenyl)pyrrolidine-3-carboxamides of piperazinecyclohexanemethylamines was synthesized and characterized for binding and function at the melanocortin-4 receptor (MC4R), and several potent benzylamine derivatives were identified. Compound 18v was found to bind MC4R with potent affinity (K_i = 0.5 nM) and high selectivity over the other melanocortin subtypes and behaved as a functional antagonist (IC₅₀ = 48 nM).     

Cadmium inhibits delta-aminolevulinate dehydratase from rat lung in vitro: interaction with chelating and antioxidant agents

The effect of cadmium (Cd(2+)) on delta-aminolevulinate dehydratase (delta-ALA-D) activity from rat lung in vitro was investigated. delta-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd(2+) in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)(2), and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelatingxantioxidant agent) was also studied. Zinc chloride (ZnCl(2)) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on delta-ALA-D activity. Cadmium inhibited rat lung delta-ALA-D activity at low concentrations. DTT (3mM), but not ZnCl(2) (100microM), protected the inhibition of enzyme activity caused by Cd(2+). Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl(2) restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of delta-ALA-D inhibition induced by Cd(2+). ZnCl(2) did not restore inhibition of enzyme activity caused by Cd(2+) plus chelating agents. Conversely, DTT restored the inhibition induced by Cd(2+)/DMSA, but not by Cd(2+)/DMPS. Antioxidants were not effective in ameliorating delta-ALA-D inhibition induced by Cd(2+), whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd(2+)xDMPSx(PhSe)(2) and Cd(2+)xDMPSxNAC was observed. There was no combined effect of Cd(2+)xchelatorxantioxidants when DMSA was used. This study demonstrated that Cd(2+)inhibited delta-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd(2+) in rat lung.     

Recent advances in natural antifungal flavonoids and their derivatives

The resistance of pathogenic fungi and failure of drug therapy increased dramatically. Numerous studies have reported the individual or synergistic antifungal potency of natural and synthesized flavonoids, especially against drug-resistant fungi. This brief review summarizes the structure and individual or synergistic antifungal activity of natural and synthesized flavonoids (literatures mainly cover the past 10 years 2009–2019), with a special focus on the antifungal spectra, structure–activity relationship and mechanisms of actions. These may contribute to a better understanding of flavonoids as multi-target agents in the treatment of mycoses and provide some ideas on the development of novel flavonoids-based antifungals.     

Microwave-assisted synthesis of novel 5-substituted benzylidene amino-2-butyl benzofuran-3-yl-4-methoxyphenyl methanones as antileishmanial and antioxidant agents

A series of 5-substitutedbenzylideneamino-2-butylbenzofuran-3-yl-4-methoxyphenyl methanones is synthesized and evaluated for antileishmanial and antioxidant activities. Compounds 4f (IC₅₀?=?52.0?±?0.09?µg/ml), 4h (IC₅₀?=?56.0?±?0.71?µg/ml) and 4l (IC₅₀?=?59.3?±?0.55?µg/ml) were shown significant antileishmanial when compared with standard sodium stibogluconate (IC₅₀?=?490.0?±?1.5?µg/ml). Antioxidant study revealed that compounds 4i (IC₅₀?=?2.44?±?0.47?µg/ml) and 4l (IC₅₀?=?3.69?±?0.44?µg/ml) have shown potent comparable activity when compared with standard ascorbic acid (IC₅₀?=?3.31?±?0.34?µg/ml). Molecular docking study was carried out which replicating results of biological activity in case of initial hits 4f and 4h suggesting that these compounds have a potential to become lead molecules in drug discovery process. In silico ADME study was performed for predicting pharmacokinetic profile of the synthesised antileishmanial agents and expressed good oral drug like behaviour.     

Meglumine as a green,efficient and reusable catalyst for synthesis and molecular docking studies of bis(indolyl)methanes as antioxidant agents

An efficient and convenient Meglumine catalyzed procedure for the synthesis of bis(indolyl) methanes at ambient temperature under aqueous conditions in high yields. The catalytic reaction proceeds very smoothly. Clean reaction, ease of product isolation/purification, easily available reactants, metal free and environmentally friendly reaction conditions are the notable advantages of the present methodology. All the entitled compounds were characterized by IR, ¹H, ¹³C NMR, mass spectra and evaluated for their antioxidant (DPPH, H₂O₂ and NO scavenging methods). They exhibited potent in vitro antioxidant activity dose-dependently. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein. 4d exhibited marked binding affinity with excellent docking score of −7.6 K.cal/mol and emerged as a lead compound.     

Optimized N-phenyl-N'-(2-chloroethyl)ureas as potential antineoplastic agents: synthesis and growth inhibition activity

In our ongoing research program aimed at the optimization of microtubule-self-assembly disrupting agents, we have prepared three series of phenylurea analogues (CEU), derived from N-(3-ω-hydroxyalkyl or 4-ω-hydroxyalkyl or 3-ω-hydroxyalkynyl)-phenyl-N′-(2-chloroethyl)ureas. Most compounds exhibit potent growth inhibitory activity on human colon carcinoma HT-29, human skin melanoma M21, and human breast carcinoma MCF-7 tumor cell lines, with a GI₅₀ ranging from 250 nM to 8 μM. Among these new molecules, three CEUs exhibit GI₅₀ in the nanomolar range. They are more potent by approximately an order of magnitude than previously described CEU analogues. As such, they are attractive hit compounds for the development of potent new alkylating antitubulin drugs.     

Design,synthesis and evaluation of carbazole derivatives as potential antimicrobial agents

Five series of novel carbazole derivatives containing an aminoguanidine, dihydrotriazine, thiosemicarbazide, semicarbazide or isonicotinic moiety were designed, synthesised and evaluated for their antimicrobial activities. Most of the compounds exhibited potent inhibitory activities towards different bacterial strains (including one multidrug-resistant clinical isolate) and one fungal strain with minimum inhibitory concentrations (MICs) between 0.5 and 16 µg/ml. Compounds 8f and 9d showed the most potent inhibitory activities (MICs of 0.5–2 µg/ml). Furthermore, compounds 8b, 8d, 8f, 8k, 9b and 9e with antimicrobial activities were not cytotoxic to human gastric cancer cell lines (SGC-7901 and AGS) or a normal human liver cell line (L-02). Structure–activity relationship analyses and docking studies implicated the dihydrotriazine group in increasing the antimicrobial potency and reducing the toxicity of the carbazole compounds. In vitro enzyme activity assays suggested that compound 8f binding to dihydrofolate reductase might account for the antimicrobial effect.     

A simple and efficient synthesis of benzimidazoles containing piperazine or morpholine skeleton at C-6 position as glucosidase inhibitors with antioxidant activity

A novel 2-(aryl)-6-morpholin-4-yl(or 4-methylpiperazin-1-yl)-1H-benzimidazole derivatives were designed and expeditiously synthesized starting from 5-morpholin-4-yl(or 4-methylpiperazin-1-yl)-2-nitroaniline with various aldehydes which were preliminarily screened for in vitro antioxidant activities and glucosidase inhibitors. The benzimidazoles were effectively synthesized by a rapid ‘onepot’ nitro reductive cyclization reaction using sodium hydrosulfite as a reagent. All reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. Antioxidant activities of the synthesized compounds were clarified using various in vitro antioxidant assays including Cupric Reducing Antioxidant Capacity (CUPRAC, ranging from 5.511 to 19.703 mM Trolox/mg compound) and Ferric Reducing Antioxidant Power (FRAP) (1.141–12.943 mM FeSO₄·7H₂O/mg compound) assays. Also, the radical scavenging activities of these compounds were assayed using ABTS⁺ and DPPH methods. The results showed that all compounds exhibited very high scavenging activity. These synthesized compounds were then evaluated for their α-glucosidase inhibitory potential and seven compounds demonstrated an inhibitory potential much better than the standard acarbose. Herein, we will provide details of the structure activity relationship of the benzimidazole analog for the potency.     

Insect kinin mimics act as potential control agents for aphids: Structural modifications of Trp4

Insect kinins are endogenous, biologically active peptides with various physiological functions. The use of insect kinins in plant protection is being evaluated by many groups. Some kinins have been chosen as lead compounds for pest control. We previously reported an insect kinin mimic IV-3 that had insecticidal activity. And by introducing a strong electron withdrawing group (-CF₃) on the benzene ring (Phe²), we discovered a compound, L ₇ , with better activity than lead IV-3 . In this work, taking L ₇ as the lead compound, we designed and synthesized 13 compounds to evaluate the influence of position 4 (Trp⁴) of insect kinin on insecticidal activity, by replacing the H atom on tryptophan with -CH₃ and -Cl or substituting the indole ring of tryptophan with the benzene, naphthalene, pyridine, imidazole, cyclohexane, and alkyl carboxamides. The aphid bioassay results showed that the compounds M ₁ , M ₃ , and M ₅ were more active than the positive control, pymetrozine. Especially, replacing the side chain by an indole ring with 4-Cl substitution ( M ₁ , LC₅₀ = 0.0029 mmol/L) increased the aphicidal activity. The structure–activity relationships (SARs) indicated that the side chain benzene ring at this position may be important to the aphicidal activity. In addition, the toxicity prediction by Toxtree, and the toxicity experiments on Apis mellifera suggested that M ₁ was no toxicity risk on a non-target organism. It could be used as a selective and bee-friendly insecticide to control aphids.     

Arylpyridines,arylpyrimidines and related compounds as potential modulator agents of the VEGF,hTERT and c-Myc oncogenes

Twenty-four derivatives structurally related to honokiol have been synthesized and biologically evaluated. IC₅₀ values were determined towards the HT-29, MCF-7 and HEK-293 cell lines. Some of these derivatives exhibited comparable or lower IC₅₀ values than honokiol towards the HT-29 and MCF-7 cell lines or else higher selectivity indexes than the natural product. Twelve selected derivatives were evaluated for their ability to inhibit the expression of the VEGFA, hTERT and c-Myc genes and also to inhibit the production of total c-Myc protein and the secretion of the VEGF protein. One of the most promising compounds, 3-(2,4-dimethoxyphenyl)pyridine, may be a good candidate for further studies as an anticancer agent as it is able to improve the effect shown by honokiol in downregulating all gene expression and protein production at a safe concentration for non-tumor cells.     

Lactulose: production, purification and potential applications

Lactulose a “bifidus factor” is composed of galactose and fructose, which can be produced by the isomerization of lactose. It is a prebiotic carbohydrate which stimulates the growth of health-promoting bacteria in the gastrointestinal tract, such as bifidobacteria and lactobacilli and at the same time inhibits growth of pathogenic bacteria such as Salmonella. It can also be used for the treatment of constipation, hepatic encephalopathy, tumour prevention, and to maintain blood glucose and insulin level. This review provides comprehensive information on the different techniques used for the production of lactulose, purification and analysis. Besides this mechanism of action and its potential applications in food and pharmaceutical industries have also been discussed.