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.     

Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors

In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl]thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by ¹H NMR, ¹³C NMR and mass spectral data and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman’s spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. The most potent AChE inhibitor was found as compound 4e (IC₅₀?=?25.5?±?2.12 µg/mL) followed by compounds 4i (IC₅₀?=?38.50?±?2.12 µg/mL), 4c (IC₅₀?=?58.42?±?3.14 µg/mL) and 4g (IC₅₀?=?68?±?2.12 µg/mL) when compared with eserine (IC₅₀?=?0.025?±?0.01 µg/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC₅₀ > 80 µg/mL). MTT assay indicated that the cytotoxic dose (IC₅₀?=?71.67?±?7.63 µg/mL) of compound 4e was higher than its effective dose.     

α-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives

The inhibitory activities of selected cyclic urea and carbamate derivatives (1–13) toward α-glucosidase (α-Gls) in in vitro assay were examined in this study. All examined compounds showed higher inhibitory activity (IC₅₀) against α-Gls compared to standard antidiabetic drug acarbose. The most potent was benzyl (3,4,5-trimethoxyphenyl)carbamate (12) with IC₅₀?=?49.85?±?0.10?µM. In vitro cytotoxicity of the investigated compounds was tested on three human cancer cell lines HeLa, A549 and MDA-MB-453 using MTT assay. The best antitumour activity was achieved with compound 2 (trans-5-phenethyl-1-phenylhexahydro-1H-imidazo[4,5-c]pyridin-2(3H)-one) against MDA-MB-453 human breast cancer cell line (IC₅₀?=?83.41?±?1.60?µM). Cyclic ureas and carbamates showed promising anti-α-glucosidase activity and should be further tested as potential antidiabetic drugs. The PLS model of preliminary QSAR study indicated that, in planing the future synthesis of more potent compounds, the newly designed should have the substituents capable of polar interactions with receptor sites in various positions, while avoiding the increase of their lipophilicity.     

Synthesis and antitumor activity of novel 2, 3-didithiocarbamate substituted naphthoquinones as inhibitors of pyruvate kinase M2 isoform

The M2 isoform of pyruvate kinase (PKM2) is a potential antitumor therapeutic target. In this study, we designed and synthesised a series of 2, 3-didithiocarbamate substituted naphthoquinones as PKM2 inhibitors based on the lead compound 3k that we previously reported. Among them, compound 3f (IC₅₀?=?1.05?±?0.17 µM) and 3h (IC₅₀?=?0.96?±?0.18 µM) exhibited potent inhibition of PKM2, and their inhibitory activities are superior to compound 3k (IC₅₀?=?2.95?±?0.53 µM) and the known PKM2 inhibitor shikonin (IC₅₀?=?8.82?±?2.62 µM). In addition, we evaluated in vitro antiproliferative effects of target compounds using MTS assay. Most target compounds exhibited dose-dependent cytotoxicity with IC₅₀ values in nanomolar concentrations against HCT116, MCF7, Hela, H1299 and B16 cells. These small molecule PKM2 inhibitors not only provide candidate compounds for cancer therapy, but also offer a tool to probe the biological effects of PKM2 inhibition on cancer cells.     

Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study

A new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b–9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the antitumour activity of all synthesized compounds 3a,b–9a,b was studied via MTT assay against two cancer cell lines (HepG2 and HCT116). Furthermore, epidermal growth factor receptor (EGFR) inhibition, using the most potent antitumour compounds, 3a, 3b, 4a, 4b, and 8a, was evaluated. The interpretation of the results showed clearly that the derivatives 3a, 4a, and 4b exhibited the highest antitumour activities against the tested cell lines HepG2 and HCT116 with IC₅₀ range of 7.7–14.2?µg/ml, in comparison with the reference drugs 5-fluorouracil (IC₅₀?=?7.9 and 5.3?µg/ml, respectively) and afatinib (IC₅₀?=?5.4 and 11.4?µg/ml, respectively). In vitro EGFR screening showed that compounds 3a, 3b, 4a, 4b, and 8a exhibited moderate inhibition towards EGFR with IC₅₀ values at micromolar levels (IC₅₀ range of 16.01–1.11?µM) compared with the reference drugs sorafenib (IC₅₀ =?1.14?µM) and erlotinib (IC₅₀ =?0.1?µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase.     

Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer,anti-cancer and anti-inflammatory activities

Abstract

In our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC₅₀?=?10.4?µM) was obtained for harmine 1 and cytotoxic activities (IC₅₀?=?0.2?µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC₅₀?=?29.2 and 55.5?µM, respectively).     

Towards lead compounds as anti-cancer agents via new phaeosphaeride A derivatives

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, К562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC₅₀?=?0.59?±?0.27?µM) was observed to be 11 times more active than PPA (IC₅₀?=?6.5?±?0.30?µM) towards the NCI-H929 cell line, with a therapeutic index of 18. Compound 6 was determined to be over half and 16 times more active than etoposide towards the NCI-H929 (IC₅₀?=?0.9?±?0.05?µM) and A549 (IC₅₀?=?100?±?7.0?µM) cell lines, respectively.     

Isolation of a new bioactive cinnamic acid derivative from the whole plant of Viola betonicifolia

A new cinnamic acid derivative was isolated from the whole plant of Viola betonicifolia as off white needle. On the basis of various modern spectroscopic techniques including HREI–MS and 1D and 2D NMR, its structure was elucidated as 2,4-dihydroxy, 5-methoxy-cinnamic acid. It showed marked inhibition against DPPH (diphenyl-2-picryl hydrazyl) free radicals with IC₅₀ = 124?±?5.76 µM. The antioxidant property of the compound was compared with α-tocopherole and vitamin C having IC₅₀ values 96?±?0.46 and 90?±?0.56 µM, respectively. In case of antiglycation assay, the compound exhibited moderate activity (IC₅₀ = 355?±?7.56 µM) similar to standard compound, rutin (IC₅₀ = 294?±?0.56 µM). However, it was non-toxic to PC-3 cell line. It is concluded that 2,4-dihydroxy, 5-methoxy-cinnamic acid has antiglycation potential which was further augmented by its antioxidant activity and thus offered an ideal natural therapeutic option for the effective management of diabetes.     

Antiplasmodial and cytotoxicity activities of some selected plants used by the Maasai community, Kenya

Malaria has continued to be a major global public health problem and a health concern in most of African countries. An estimated 350–500 million cases of malaria each year result in about one million deaths, mainly children under five. The rate of malaria infection is increasing rapidly partly due to drug resistance by the Plasmodium falciparum. The cost of the current drugs is prohibitive to the poor. There is therefore urgent need to identify new antimalarial agents that are effective, safe and affordable. In our continuous search for these new antimalarial compounds, extracts from five medicinal plants from the Maasai community in Kenya were tested against P. falciparum (D6; chloroquine sensitive and W2; chloroquine resistant strains). Of the tested total plant extracts, 5 crude extracts showed good antiplasmodial activity against D6 strain of P. falciparum with IC₅₀ values lower or equal to 14.3 μg/ml, 2 were moderately active with IC₅₀ values in between 26.6 and < 50 μg/ml. The petroleum ether extracts of the aerial parts and roots of Fuerstia africana demonstrated high antiplasmodial activity against the chloroquine sensitive antiplasmodial strain D6 (IC₅₀ 1.5 and 4.6 μg/ml, respectively with a selectivity index of 44 against vero cells). Manilkara discolor also exhibited promising antiplasmodial activity especially against D6 (IC₅₀ 11.5 and 26.6 μg/ml). In addition, ethyl acetate extract of the roots of Pentas lanceolata and the aerial parts of Sericocomopsis hildebrandtii demonstrated moderate antiplasmodial activity against D6 and W2 (IC₅₀ 14.3 and 16.51 μg/ml) respectively. F. africana therefore has high potential and can be pursued for the development of an antimalarial drug.     

Ultrasonic synthesis of tyramine derivatives as novel inhibitors of α-glucosidase in vitro

Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC₅₀?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC₅₀?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC₅₀ values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.     

Design,synthesis and biological evaluation of novel L-isoserine tripeptide derivatives as aminopeptidase N inhibitors

Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, one compound 16l (IC₅₀?=?2.51?±?0.2 µM) showed similar inhibitory effect compared with control compound Bestatin (IC₅₀?=?6.25?±?0.4 µM) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.     

Design,synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment

Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodone-tacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT_1A agonist activities (1d, EC₅₀?=?0.36?±?0.08?nM; 2a, EC₅₀?=?0.58?±?0.14?nM) and 5-HT reuptake inhibitory activities (1d, IC₅₀?=?20.42?±?6.60?nM; 2a, IC₅₀?=?22.10?±?5.80?nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC₅₀?=?1.72?±?0.217?μM, BuChE IC₅₀?=?0.34?±?0.03?μM; 2a, AChE IC₅₀?=?2.36?±?0.34?μM, BuChE IC₅₀?=?0.10?±?0.01?μM). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment.     

Characterization of nimbidiol as a potent intestinal disaccharidase and glucoamylase inhibitor present in Azadirachta indica (neem) useful for the treatment of diabetes

Azadirachta indica, used in antidiabetic herbal drugs, was reported to contain α-glucosidase inhibitor. Bioassay guided purification characterized the inhibitor as nimbidiol (a diterpenoid), present in root and stem-bark of the tree. Nimbidiol inhibited intestinal (mammalian) maltase-glucoamylase, sucrase-isomaltase, lactase, trehalase and fungal α-glucosidases. Nimbidiol showed a mixed competitive inhibition on intestinal carbohydrases. IC₅₀, Ki and Ki′ (µM) were 1.35 ± 0.12, 0.08 ± 0.01, 0.25 ± 0.11, respectively, for maltase-glucoamylase (maltotetraose as substrate). Nimbidiol was more potent inhibitor of isomaltase (IC₅₀ 0.85 ± 0.035 µM), lactase (IC₅₀ 20 ± 1.33 µM) and trehalase (IC₅₀ 30 ± 1.75 µM) than acarbose, voglibose, salacinol, kotalanol and mangiferin. Ki and Ki′ values (µM) for intestinal sucrase were 0.7 ± 0.12 and 1.44 ± 0.65, respectively. Development of nimbidiol as an antidiabetic drug appears to be promising because of broad inhibition spectrum of intestinal glucosidases and easy synthesis of the molecule.     

Synthesis,biological evaluation,and molecular modelling of new naphthalene-chalcone derivatives as potential anticancer agents on MCF-7 breast cancer cells by targeting tubulin colchicine binding site

Abstract

A series of naphthalene-chalcone derivatives (3a–3t) were prepared and evaluated as tubulin polymerisation inhibitor for the treatment of breast cancer. All compounds were evaluated for their antiproliferative activity against MCF-7 cell line. The most of compounds displayed potent antiproliferative activity. Among them, compound 3a displayed the most potent antiproliferative activity with an IC₅₀ value of 1.42?±?0.15?µM, as compared to cisplatin (IC₅₀?=?15.24?±?1.27?µM). Additionally, the promising compound 3a demonstrated relatively lower cytotoxicity on normal cell line (HEK293) compared to tumour cell line. Furthermore, compound 3a was found to induce significant cell cycle arrest at the G₂/M phase and cell apoptosis. Compound 3a displayed potent tubulin polymerisation inhibitory activity with an IC₅₀ value of 8.4?µM, which was slightly more active than the reference compound colchicine (IC₅₀?=?10.6?µM). Molecular docking analysis suggested that 3a interact and bind at the colchicine binding site of the tubulin.     

New quinoxalinone inhibitors targeting secreted phospholipase A2 and α-glucosidase

Elevated blood glucose and increased activities of secreted phospholipase A2 (sPLA2) are strongly linked to coronary heart disease. In this report, our goal was to develop small heterocyclic compound that inhibit sPLA2. The title compounds were also tested against α-glucosidase and α-amylase. This array of enzymes was selected due to their implication in blood glucose regulation and diabetic cardiovascular complications. Therefore, two distinct series of quinoxalinone derivatives were synthesised; 3-[N′-(substituted-benzylidene)-hydrazino]-1H-quinoxalin-2-ones 3a–f and 1-(substituted-phenyl)-5H-[1,2,4]triazolo[4,3-a]quinoxalin-4-ones 4a–f. Four compounds showed promising enzyme inhibitory effect, compounds 3f and 4b–d potently inhibited the catalytic activities of all of the studied proinflammatory sPLA2. Compound 3e inhibited α-glucosidase (IC₅₀?=?9.99?±?0.18 µM); which is comparable to quercetin (IC₅₀?=?9.93?±?0.66 µM), a known inhibitor of this enzyme. Unfortunately, all compounds showed weak activity against α-amylase (IC₅₀?>?200 µM). Structure-based molecular modelling tools were utilised to rationalise the SAR compared to co-crystal structures with sPLA2-GX as well as α-glucosidase. This report introduces novel compounds with dual activities on biochemically unrelated enzymes mutually involved in diabetes and its complications.     

In Vitro Anticancer Activity of Staphyloxanthin Pigment Extracted from <Emphasis Type="Italic">Staphylococcus gallinarum</Emphasis> KX912244, a Gut Microbe of <Emphasis Type="Italic">Bombyx mori</Emphasis>

The present study reports the in vitro biological nature of the pigment produced by Staphylococcus gallinarum KX912244, isolated as the gut microflora bacterium of the insect Bombyx mori. The purified pigment was characterized as Staphyloxanthin based on bio-physical characterization techniques like Fourier transform infrared spectroscopy, high performance liquid chromatography, Proton nuclear magnetic resonance spectroscopy (¹H NMR), Liquid chromatography-Mass spectroscopy and Gas chromatography-Mass spectroscopy. The Staphyloxanthin pigment presented considerable biological properties including in vitro antimicrobial activity against pathogens Staphylococcus aureus, Escherichia coli and Candida albicans; in vitro antioxidant activity by % DPPH free radical scavenging activity showing IC₅₀ value of 54.22 µg/mL; DNA damage protection activity against reactive oxygen species and anticancer activity evaluated by cytotoxicity assay against 4 different cancer cell lines like the Dalton’s lymphoma ascites with IC₅₀ value 6.20?±?0.02 µg/mL, Ehrlich ascites carcinoma having IC₅₀ value 6.48?±?0.15 µg/mL, Adenocarcinomic human alveolar basal epithelial cells (A549 Lung carcinoma) bearing IC₅₀ value 7.23?±?0.11 µg/mL and Mus mucus skin melanoma (B16F10) showing IC₅₀ value 6.58?±?0.38 µg/mL and less cytotoxicity towards non-cancerous human fibroblast cell lines (NIH3T3) with IC₅₀ value of 52.24 µg/mL. The present study results suggest that Staphyloxanthin acts as a potential therapeutic agent especially due to its anticancer property.     

Indole and aminoimidazole moieties appear as key structural units in antiplasmodial molecules

From a library of compounds of natural sources, a big series of molecules was chosen by random sampling to evaluate their in vitro antimalarial activity against Plasmodium falciparum and their antifungal activity against Candida sp. From 184 molecules tested, no molecules were active against Candida sp. (MIC > 10 μg/ml) whereas 13 clearly showed high antiplasmodial activity in vitro, with an IC₅₀ less than 1 μg/ml against the chloroquine-resistant strain of P. falciparum FcM29-Cameroon. The molecules with the best antiplasmodial efficacy were 10-hydroxy-ellipticin (IC₅₀: 0.08 μg/ml), tchibangensin (IC₅₀: 0.13 μg/ml), ellipticin hydrochloride (IC₅₀: 0.17 μg/ml), usambarensin (IC₅₀: 0.23 μg/ml), 7S,3S-ochropposinine oxindole (IC₅₀: 0.25 μg/ml), 3,14-dihydro-ellipticin (IC₅₀: 0.25 μg/ml), tetrahydro-4′,5′,6′17-usambarensin 17S (IC₅₀: 0.26 μg/ml), ellipticine (IC₅₀: 0.28 μg/ml), aricin (IC₅₀: 0.3 μg/ml), 10-methoxy-ellipticin (IC₅₀: 0.32 μg/ml), aplysinopsin (IC₅₀: 0.43 μg/ml), descarbomethoxydihydrogambirtannin (IC₅₀: 0.46 μg/ml) and ochrolifuanin A (IC₅₀: 0.47 μg/ml). Among these 13 promising molecules, all except descarbomethoxydihydrogambirtannin, ochrolifuanine A and usambarensine presented here novel biological activities since they had never been described in the literature for their antiplasmodial activity. In spite of the large diversity of the molecules which have been tested, it is interesting to note that the ones active against Plasmodium are all indole derivatives (and one is both indolic and aminoimidazolic). To find new antiplasmodial compounds, ethnopharmacological approaches studying traditional medicine treatments for malaria is largely used but random research produced here an interesting yield (7%) of new antiplasmodial hits and appears therefore complementary to the traditional medicine way.     

Antioxidative iridoid glycosides from the sky flower (Duranta repens Linn)

Phytochemical investigations were performed on the EtOAc-soluble fraction of the whole plant of the sky flower (Duranta repens) which led to the isolation of the iridoid glycosides 1–6. Their structures were elucidated by both 1D and 2D NMR spectroscopic analysis. All the compounds showed potent antioxidative scavenging activity in four different tests, with half maximal inhibitory concentration (IC₅₀) values in the range 0.481–0.719?mM against DPPH radicals, 4.07–17.21 µM for the hydroxyl radical (^?OH) inhibitory activity test, 43.3–97.37 µM in the total reactive oxygen species (ROS) inhibitory activity test, and 3.39–18.94 µM in the peroxynitrite (ONOO^?) scavenging activity test. Duranterectoside A (1) displayed the strongest scavenging potential with IC₅₀ values of (0.481?±?0.06?mM, 4.07?±?0.03, 43.30?±?0.05, 3.39?±?0.02?µM) for the DPPH radicals, ^?OH inhibitory activity test, total ROS inhibitory activity test and the ONOO^? scavenging activity test, respectively.     

Antiplasmodial flavanones and a stilbene from Carpha glomerata

Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C), 4 (carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3″-hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product. All structures were elucidated based on analyses of their HR-ESIMS and 1D and 2D NMR data. Compounds 1, 2, and 6, which have prenyl or hydroxyprenyl side chains, exhibited antiplasmodial activities with IC₅₀ values of 5.2?±?0.6, 3.4?±?0.4, and 6.7?±?0.8?µM against the drug-resistant Dd2 strain of Plasmodium falciparum. In addition the prenylated stilbene 5 also showed good activity, with IC₅₀ 5.8?±?0.7?µM.     

Phytochemical analysis and evaluation of antioxidant and anti-acetylcholinesterase activities of Euphorbia dendroides L. (Euphorbiaceae) latex

The aim of this study was to evaluate the antioxidant and anti-acetylcholinesterase properties and phytochemical constituents of the latex from Euphorbia dendroides L. (Euphorbiaceae) growing wild in Sicily. Phytochemical analysis revealed that into E. dendroides latex the triterpenoids were the most abundant among the identified compounds. Furthermore, a high content of polyphenols mainly as phenolic acids, was found. The antioxidant and free-radical scavenging properties, by several in vitro assays such as DPPH, TEAC and FRAP, have been evaluated. The results showed that E. dendroides latex has significant antioxidant activity, as measured by DPPH assay (2927.01?±?98.03 µmols of Trolox equivalent (TE)/100g FW). Reactivity towards ABTS radical cation and ferric-reducing antioxidant power (FRAP) values were 7580.95?±?97.65 µmols of TE/100g FW and 4383.13?±?95.30?μmol of TE/100g FW, respectively. The latex exhibited also significant inhibition of acetylcholinesterase activity with an IC₅₀ value of 4.46 µg/mL (C.L.?=?2.002–9.947). Furthermore, Brine shrimp (Artemia salina) cytotoxicity bioassay showed that the larvae viability was significantly affected at higher concentrations than those capable to induce significant antioxidant and anti-acetylcholinesterase effects (LD₅₀ 25 µg/mL). The results suggest that polyphenols and terpenoids can contribute significantly to antioxidant and anti-acetylcholinesterase activities of E. dendroides latex.