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In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone–carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode. [ABSTRACT FROM AUTHOR]

Enicostemma hyssopifolium is a perineal herb widely used as an antidiabetic agent in folklore medicine. The present work was focused on the assessment of its antiinflammatory and cytotoxic properties. Its methanolic extract was evaluated for antiinflammatory activity using murine monocytic macrophage RAW 264.7 cells, and screened for its cytotoxic property in different cancer cell lines. The methanolic extract was able to potentially inhibit the bacterial lipopolysaccharides-induced inflammatory response in RAW 264.7 cells. Results of the cytotoxicity studies revealed that the methanolic extract effectively induced the cytotoxicity at considerably lower concentration in MCF-7, A-549, and COLO-205 cell lines, while the viability of HeLa, CasKi, and HT-29 cells were inhibited at comparatively higher concentrations. Results thus indicated that E. hyssopifolium possessed potent anti-inflammatory and cytotoxic properties. This necessitates further exploration of bioactive phytochemical compounds responsible for these properties for therapeutic applications. [ABSTRACT FROM AUTHOR]

New methyl-substituted, and diphenyl-substituted fused dipyranoquinolinones are prepared in excellent yields via the triple bond activation and 6-endo-dig cyclization of propargyloxycoumarin derivatives by gold nanoparticles supported on TiO2 in chlorobenzene under microwave irradiation. In the absence of gold nanoparticles, the methyl-substituted propargyloxycoumarin derivatives resulted in fused furopyranoquinolinones through Claisen rearrangement and 5-exo-dig cyclization. The intermediate propargyloxy-fused pyridocoumarins are prepared by propargylation of the corresponding hydroxy-fused pyridocoumarins. The methyl-substituted derivatives of the latter are synthesized in excellent yield by the three-component reaction of amino hydroxycoumarin with n-butyl vinyl ether under iodine catalysis. The diphenyl-substituted derivatives of hydroxy-fused pyridocoumarins are obtained, also, by the three-component reaction of amino hydroxycoumarin with benzaldehyde and phenyl acetylene catalyzed by iron (III) chloride. Preliminary biological tests of the title compounds indicated lipoxygenase (LOX) (EC 1.13.11.12) inhibitory activity (60–100 μM), whereas compound 28a, with IC50 = 10 μM, was found to be a potent LOX inhibitor and a possible lead compound. Only compounds 10b and 28b significantly inhibited lipid peroxidation. [ABSTRACT FROM AUTHOR]

In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone–carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode.

The effect of extracting solvents used by two methods on the TPC, TFC, antioxidant as well as lipoxygenase, and tyrosinase inhibition activities of O. ficus-indica fruit (peel and pulp) were studied. The results manifest that extracts with solvent polarities showed different levels of polyphenols contents and antioxidant activities. The extracts acquired by the Soxhlet method were the most fascinating. Interestingly, peel extracts contain more polyphenols than pulp and showed activities. Lipoxygenase and tyrosinase inhibitory activity of the fruit peel and pulp extracts was reported for the first time. The promising results obtained prompted to the formulation of a stable phytocosmetic emulsion system loaded with 1% pre-concentrated peel extract, aiming to revive facial skin properties. The efficacy of the formulations was determined through SPF and UVA protection factors. To the in vitro safety assessment CAM-TBS, HET-CAM, and red blood cell tests were achieved. Importantly, the formulation did not induce any toxicity. [ABSTRACT FROM AUTHOR]

Truffles are natural food product very famous for its health benefits for being significant biosource of essential fatty acids, proteins and other antioxidant and phenolic compounds. The current study was conducted to evaluate the phytochemicals, antioxidant and lipoxygenase inhibition activities of Terfezia boudieri of Saudi origin. Various phytochemicals were screened applying standard procedures. The total methanol extract (TME) of the truffle was subjected to several chromatographic procedures. The antioxidant activity was evaluated by DPPH antioxidant procedure, comparing results with trolox as standard. Results demonstrated that Terfezia boudieri chemically characterized by the availability of various constituents such as flavonoids, steroids, saponins, tannins and carbohydrates at different levels. Phytochemical investigation led to the isolation of β-sitosterol and gallic acid that were identified using ¹H, 13C, DEPT, COSY, HMQC and HMBC NMR spectroscopic data. Results demonstrated high antioxidant activity with IC50: 50.4 µg/ml and 31.4 µg/ml for TME and gallic acid, respectively. TME and gallic acid exhibited lipoxygenase inhibitory activity with IC50 values 4.59 and 0.53 µg/ml for TME and gallic acid, respectively. The higher lipoxygenase inhibitory activity was presumably correlated to the high antioxidant activity. In conclusion, current investigation confirms the folklore use of Terfezia boudieri as antinflammatory food. Hence, the studied Terfezia boudieri may have a great potential as antioxidant and antinflammatory functional food and nutraceuticals products for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Consumption of green leafy vegetables, a nutrient-dense food, is associated with protective roles in human health and a reduction in risk of cancer, cardiovascular, and other inflammatory diseases. Phytochemical components such as phenolics and flavonoids are said to contribute to these benefits. Data on the anti-inflammatory potential and phenolic content of many Indian green leafy vegetables is still scanty. We investigated eleven tropical green leafy vegetables for their phenolic and flavonoid content along with anti-inflammatory and free radical scavenging properties. Black nightshade had the lowest phenolic and flavonoid content (2.36 mg Gallic Acid Equivalents/g DW and 1.66 mg Rutin Equivalents/g DW), whereas desert horsepurslane (41.73 mg GAE/g DW) and red amaranth (27.18 mg RE/g DW) had the highest phenolic and flavonoid content, respectively. Similarly, the free radical scavenging activity for 2, 2-diphenyl-1-picrylhydrazyl (DPPH) ranged from 10.57 – 84.97 % inhibition and 50.73 – 266.48 µg Trolox Equivalents/g DW for 2, 2-azinobis-(3-ethylbenzothiazoline6-sulphonate (ABTS) decolorization assay. The phenolic and flavonoid content correlated significantly with the radical scavenging activity. The hemolysis and lipoxygenase inhibition was observed to be lowest in Amaranthus sp. and desert horsepurslane (6.08% and 53.75 %) and highest in dill and fenugreek (69.94% and 78.55 %), respectively. Overall, our study adds to the polyphenolic and antioxidant data available on green leafy vegetables, in addition to highlighting their anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

The synthesis of derivatives of three nonspecific COX-1 and COX-2 inhibitors, ibuprofen, ketoprofen, naproxen is presented. These acids were connected via an amide bond with an amino acid (L-proline, L-tyrosine, and beta-alanine) used as a linker. The amino acid carboxylic group was esterified with 3,4,5 trimethoxybenzyl alcohol. The activity of the novel derivatives was examined in vivo on carrageenan-induced inflammation, and in vitro, as cyclooxygenase and lipoxygenase inhibitors. It was found that the new compounds were more potent anti-inflammatory agents than the parent drugs. Thus, the ibuprofen (21) and ketoprofen (16) derivatives reduced rat paw edema by 67 and 91% (the reduction by the relevant NSAIDs was 36 and 47%, respectively). They inhibited COX-2 more than the starting drugs (21 by 67%, ibuprofen 46%, 19 by 94%, ketoprofen 49%). Docking of compounds on the active sites of COX-1 and COX-2 reflects their in vitro activity. Thus, 19 adopts an unfavorable orientation for COX-1 inhibition, but it binds effectively in the binding pocket of COX-2, in agreement with the absence of activity for COX-1 and the high inhibition of COX-2. In conclusion, the performed structural modifications result in the enhancement of the anti-inflammatory activity, compared with the parent NSAIDs. [ABSTRACT FROM AUTHOR]

Trigonella foenum-graecum L. (fenugreek) leaves are nutritionally rich green leafy vegetables consumed in South-East Asian and Middle-Eastern countries. Scientific data suggests properties including anti-inflammatory, antipyretic, anti-nociception, and hepatoprotective. However, the molecules responsible for these properties are yet to be identified. In the present study, we have isolated and characterized an anti-inflammatory nutraceutical molecule based on bioassay from the fresh leaves of fenugreek. The lipoxygenase inhibition assay revealed 79.9 ± 1.1% and 69.0 ± 2.9% inhibition in ethanolic and aqueous extracts, respectively. The ethanolic extract purified on a semi-prep HPLC column yielded a nutraceutical molecule quercetin glycoside (QG) having potent inhibition of lipoxygenase (75.3 ± 1.6%) at 10 mM and hyaluronidase (67.4 ± 4.0%) at 2 mM, respectively. The QG structure was elucidated by spectroscopic data, including FTIR, UHPLC-MS/MS, and 1D and 2D NMR as Quercetin-3-O-diglucoside-7-O-glucoside. QG also suppressed ROS, NO, and IL-6 production in LPS stimulated RAW264.7 cells. Radical scavenging assays of DPPH and ABTS revealed the potent antioxidant activity of QG with an EC50 of 245.5 and 68.8 μM, respectively. Our results demonstrate that newly characterized quercetin glycoside from fresh leaves of fenugreek possesses potential anti-inflammatory and antioxidant activities.

Ranunculus muricatus L., an important member of family Ranunculaceae upon submission to phytochemical studies, led to the isolation of a novel natural hydrazine derivative, muricazine (1). Chemical structure of the compound was established with the aid of advanced spectroscopic techniques. It was evaluated for in vitro antioxidant, lipoxygenase, and urease (jack-bean) inhibitory activities. Results suggested that compound 1 could scavenge the DPPH free radical (42.1 ± 0.12 μM) to a great extent as compared to the standard (40.6 ± 0.91 μM). However, it showed moderate inhibitory potential against lipoxygenase (65.2 ± 0.45 μM) and urease (54.8 ± 0.23 μM) enzymes. [ABSTRACT FROM AUTHOR]

Muriolide (1), a new aromatic lactone, has been isolated from the ethyl acetate fraction of Ranunculus muricatus. The compound was structurally characterized with the help of UV, IR, mass, 1D- and 2D-NMR data. It was tested in vitro for antioxidant and lipoxygenase inhibitory potential. Compound 1 showed good DPPH radical scavenging activity (IC50=56.9 μM), however it was moderately active against lipoxygenase enzyme (IC50=68.3 μM). [ABSTRACT FROM AUTHOR]

A novel series of coumarin derivatives linked to the N-benzyl triazole group were synthesized and evaluated against 15-lipoxygenase (15-LOX), and acetyl- and butyrylcholinesterase (AChE and BuChE) to find the most potent derivative against Alzheimer’s disease (AD). Most of the compounds showed weak to moderate activity against ChEs. Among the most active BuChE and 15-LOX inhibitors, 8l and 8n exhibited an excellent neuroprotective effect, higher than the standard drug (quercetin) on the PC12 cell model injured by H2O2 and significantly reduced aggregation of amyloid Aβ1-42, with potencies of 1.44 and 1.79 times higher than donepezil, respectively. Compound 8l also showed more activity than butylated hydroxytoluene (BHT) as the reference antioxidant agent in reducing the levels of H2O2 activated by amyloid β in BV2 microglial cells. Kinetic and ligand–enzyme docking studies were also performed for better understanding of the mode of interaction between the best BuChE inhibitor and the enzyme. Considering the acceptable BuChE and 15-LOX inhibition activities as well as significant neuroprotection, and anti-amyloid aggregation activities, 8l and 8n could be considered as potential MTDLs for further modification and studies against AD.

Azima tetracantha, a traditional medicinal plant included in the order Brassicales and family Salvadoraceae, is widely used as a dietary supplement in folklore medicines. The plant is also used for the treatment of rheumatism, diarrhea and other inflammatory disorders. The present investigation focused on the phytochemical composition, radical scavenging, reducing potential and anti-proliferative activities of the A. tetracantha leaves. Quantitative estimation of the polyphenols and flavonoids revealed significantly elevated levels in the methanol extract. Corroborating with this, methanol extract exhibited higher in vitro anti-radical scavenging effect against 2,2-diphenyl-1- picrylhydrazyl (34.14 ± 2.19 μg/mL), and hydrogen peroxide (44.96 ± 1.77 μg/mL), as well as ferric reducing properties (58.24 ± 6.98 μg/mL). The methanolic extract also showed strong lipoxygenase (71.42 ± 6.36 μg/mL) and nitric oxide inhibitory activities (94.23 ± 8.11 μg/mL). Cytotoxic activity against MCF7 cells was found to be higher (IC50= 37.62 ± 2.94 μg/mL), than that of MDAMB231 cells (IC50= 69.11 ± 5.02 μg/mL). The qPCR-based analysis indicated dose-dependent increase in the expression of the pro-apoptotic genes such as executioner caspases and apoptotic protease activating factor-1. Overall, the results indicated the possible use of methanol extract of A. tetracantha leaves as a chain-breaking antioxidant molecule and are capable of inhibiting inflammatory enzymes and the proliferative potential of breast cancer cells. [ABSTRACT FROM AUTHOR]

Mushrooms have great potential to be used as food and pharmaceutical sources. Most of the non-edible mushrooms contain biologically active metabolites that are functional for modern medicinal applications. Within the present study, anticoagulant and antiinflammatory activities of Geastrum fimbriatum Fr. (Syn. Geastrum sessile (Sowerby) Pouzar), a mushroom naturally grown in Turkey, were investigated. The in vitro anticoagulant activity of the ethanolic extract obtained with a soxhlet apparatus determined by activated partial thromboplastin time (APTT) and prothrombin time (PT) assays using commercial reagents. The antiinflammatory activity of the extract was determined by lipoxygenase inhibition assay. When compared with the negative control DMSO, G. fimbriatum extract exhibited significant anticoagulant effects in the APTT test that evaluates the intrinsic coagulation pathway. The ethanolic extract found to prolong the coagulation time. However, no inhibition was observed in the PT test which evaluates the extrinsic coagulation pathway, The extract showed 12.92% inhibition on the lipoxygenase enzyme activity. Overall, G. fimbriatum ethanolic extract exhibited potent antiinflammatory activity besides being a potential source of anticoagulant. Further analysis is required to evaluate the medical use of Geastrum mushrooms from a pharmaceutical point of view.

The synthesis of derivatives of three nonspecific COX-1 and COX-2 inhibitors, ibuprofen, ketoprofen, naproxen is presented. These acids were connected via an amide bond with an amino acid (L-proline, L-tyrosine, and beta-alanine) used as a linker. The amino acid carboxylic group was esterified with 3,4,5 trimethoxybenzyl alcohol. The activity of the novel derivatives was examined in vivo on carrageenan-induced inflammation, and in vitro, as cyclooxygenase and lipoxygenase inhibitors. It was found that the new compounds were more potent anti-inflammatory agents than the parent drugs. Thus, the ibuprofen (21) and ketoprofen (16) derivatives reduced rat paw edema by 67 and 91% (the reduction by the relevant NSAIDs was 36 and 47%, respectively). They inhibited COX-2 more than the starting drugs (21 by 67%, ibuprofen 46%, 19 by 94%, ketoprofen 49%). Docking of compounds on the active sites of COX-1 and COX-2 reflects their in vitro activity. Thus, 19 adopts an unfavorable orientation for COX-1 inhibition, but it binds effectively in the binding pocket of COX-2, in agreement with the absence of activity for COX-1 and the high inhibition of COX-2. In conclusion, the performed structural modifications result in the enhancement of the anti-inflammatory activity, compared with the parent NSAIDs.

Trigonella foenum-graecum L. (fenugreek) leaves are nutritionally rich green leafy vegetables consumed in South-East Asian and Middle-Eastern countries. Scientific data suggests properties including anti-inflammatory, antipyretic, anti-nociception, and hepatoprotective. However, the molecules responsible for these properties are yet to be identified. In the present study, we have isolated and characterized an anti-inflammatory nutraceutical molecule based on bioassay from the fresh leaves of fenugreek. The lipoxygenase inhibition assay revealed 79.9 ± 1.1% and 69.0 ± 2.9% inhibition in ethanolic and aqueous extracts, respectively. The ethanolic extract purified on a semi-prep HPLC column yielded a nutraceutical molecule quercetin glycoside (QG) having potent inhibition of lipoxygenase (75.3 ± 1.6%) at 10 mM and hyaluronidase (67.4 ± 4.0%) at 2 mM, respectively. The QG structure was elucidated by spectroscopic data, including FTIR, UHPLC-MS/MS, and 1D and 2D NMR as Quercetin-3-O-diglucoside-7-O-glucoside. QG also suppressed ROS, NO, and IL-6 production in LPS stimulated RAW264.7 cells. Radical scavenging assays of DPPH and ABTS revealed the potent antioxidant activity of QG with an EC50 of 245.5 and 68.8 μM, respectively. Our results demonstrate that newly characterized quercetin glycoside from fresh leaves of fenugreek possesses potential anti-inflammatory and antioxidant activities. [ABSTRACT FROM AUTHOR]

Searching the organic compound as anti‐inflammatory agent is a fruitful effort to treat inflammatory disorders such as asthma, arthritis, psoriasis, and especially cancer. These disorders can be cured by lipoxygenase (LOX) inhibitors, which have the ability to stop the development and progression of inflammation. The present research described the synthesis of fifteen new N‐alkyl/aralkyl/aryl derivatives (7 a–o) of 2‐(4‐ethyl‐5‐(1‐phenylcarbamoyl)piperidine‐4H‐1,2,4‐triazol‐3‐ylthio)acetamide by the continuous conversions of ethyl piperidine‐4‐carboxylate (a) into phenylcarbamoyl derivative (1) hydrazide (2), semicarbazide (3) and finally the N‐ethylated 5‐(1‐phenylcarbamoyl)piperidine‐1,2,4‐triazole (4). The target molecules (7 a–o) were formed by the reaction of 4 with various electrophiles (6 a–o), in methanolic potassium hydroxide. These synthetic analogues were characterized by FTIR, 1H, 13C NMR spectroscopy, EIMS, and HREIMS spectrometry. The compounds 7 a–o were screened for their inhibitory potential against 15‐lipoxygenase. Compounds 7 b, 7 e, 7 c and 7 g displayed the potent inhibitory potential (IC50 17.52±0.67, 35.61±0.81, 36.24±0.83 & 36.52±0.58 μM, respectively), whereas, moderate inhibition was shown by 7 h, 7 a, 7 d with IC50 values between 42.95±0.73 to 45.67±0.75 μM, respectively. Some compounds exhibited drug‐like characteristics due to their lower cytotoxic and good ADME profiles and supported by molecular modeling studies where one of the NH groups was found engaged through hydrogen bonding with Ala672. The carbonyl group amide and Asn554 were connected by a hydrogen bond, whereas the second NH group was also linked through hydrogen bonds with Gln363. [ABSTRACT FROM AUTHOR]

The new binuclear antimony(III) complexes corresponding to the formulas [SbCl3(µ2-S)(MtMBZIM)2]2 (1), {[SbBr2(µ2-Br)(MtMBZIM)2]2·H2O} (2) and {[SbI2(µ2-I)(MtMBZIM)2]2·H2O} (3) (MtMBZIM: 5-methoxy-2-mercaptobenzimidazole) have been synthesized and structurally characterized with regard to their melting point, elemental analysis, molar conductivity, FT-IR, and FT-Raman spectroscopic techniques, and TG-DTA analysis. The crystal structures of 1-3 have been determined by single-crystal X-ray diffraction. Compounds 1-3 are doubly bridged dimers and in each square pyramidal monomeric unit, the equatorial plane is formed by two sulfur and two halogen atoms in trans-S, trans-X arrangement. The monomeric units in 2 and 3 are linked to each other via halogen bridges, but in 1, they are linked to each other via sulfur bridges; to our knowledge, this binding type is the first example of trans-S, trans-X square pyramidal antimony(III) complexes. Newly synthesized complexes with their corresponding ligand have been tested for their in vitro cytotoxic activity against human adenocarcinoma cervix (HeLa) cells as well as for their antimicrobial activity. The influence of 1-3 on the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX) has been determined experimentally and theoretically. [ABSTRACT FROM AUTHOR]

Background: Heliotropium europaeum L. is known to contain pyrrolizidine alkaloids and possesses a wide variety of biological activities. Objective: The objective of the study was to discover antioxidant phytochemical compounds in H. europaeum and assess their in vitro lipoxygenase (LOX)- and angiotensin-converting enzyme (ACE) inhibitory activities. Materials and Methods: H. europaeum herbs were extracted exhaustively by maceration using 90% aqueous ethanol. Solvent fractionation with n-hexane, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol was performed with the dried extract until complete exhaustion. Two antioxidant active fractions (CH2Cl2and EtOAc) were combined and subjected to medium pressure liquid chromatography followed by reversed-phase high-performance liquid chromatography. Quantitative evaluation in terms of the antioxidant activities of the isolated compounds was performed using the 2,2-diphenyl-1-picrylhydrazyl assay. The potential limiting effects on the action of ACE and soybean LOX were assessed quantitatively. Results: Isolates of eight newly identified phenolic compounds from H. europaeum exhibited antioxidant and ACE- and LOX-inhibitory activities. The isolated compounds were identified as kaempferol (1), luteolin (2), quercetin (3), kaempferol-3-O-glucoside (4), and luteolin-7-O-glucoside (5), in addition to caffeic acid (6), rosmarinic acid (7), and methyl rosmarinate (8). Among the isolated compounds, quercetin possessed the most potent antioxidant activity (IC50= 8.1 μM) and ACE-inhibitory activity (IC50= 17.5 μM), whereas rosmarinic acid and its methyl ester showed the strongest LOX-inhibitory activity (IC50s = 4.2 μM and 3.6 μM, respectively). Conclusion: Our study is the first report on the phenolic constituents of the H. europaeum herbal extract and their biological activities. A total of eight phenolics were identified in this extract and isolated for the first time. Our results on H. europaeum extract constituents provide some scientific evidence on the beneficial effects of its traditional uses. [ABSTRACT FROM AUTHOR]

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. In silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.

A series of L-serine amides of antioxidant acids, such as Trolox, (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid (phenolic derivative of cinnamic acid) and 3,5-di-tert-butyl-4-hydroxybenzoic acid (structurally similar to butylated hydroxytoluene), was synthesized. The hydroxy group of serine was esterified with two classical NSAIDs, ibuprofen and ketoprofen. The Trolox derivatives with ibuprofen (7) and ketoprofen (10) were the most potent inhibitors of lipid peroxidation (IC50 3.4 μΜ and 2.8 μΜ), several times more potent than the reference Trolox (IC50 25 μΜ). Most of the compounds decreased carrageenan-induced rat paw edema (37–67% at 150 μmol/kg). They were moderate inhibitors of soybean lipoxygenase, with the exception of ibuprofen derivative 8 (IC50 13 μΜ). The most active anti-inflammatory compounds exhibited a significant decrease in lipidemic indices in the plasma of Triton-induced hyperlipidemic rats, e.g., the most active compound 9 decreased triglycerides, total cholesterol and low-density lipoprotein cholesterol by 52%, 61% and 70%, respectively, at 150 μmol/kg (i.p.), similar to that of simvastatin, a well-known hypocholesterolemic drug. Since the designed compounds seem to exhibit multiple pharmacological actions, they may be of use for the development of agents against inflammatory and degenerative conditions.

The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological activities. The synthesis of the pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid. The compounds are obtained in good yields 68–99% and their structure was confirmed using IR, 1H-NMR, 13C-NMR and elemental analysis. The novel derivatives were studied in vitro for their antioxidant, anti-lipid peroxidation (AAPH) activities and inhibitory activity of lipoxygenase. Both classes strongly inhibit lipid peroxidation. Compound 2g was the most potent lipoxygenase inhibitor (IC50 = 80 µM). The inhibition of the carrageenin-induced paw edema (CPE) and nociception was also determined, with compounds 2d and 2e being the most potent. Compound 2e inhibited nociception higher than 2d. Pyrazoline 2d was found to be active in a preliminary test, for the investigation of anti-adjuvant-induced disease (AID) activity. Pyrazoline derivatives were found to be more potent than pyrazoles. Docking studies of the most potent LOX inhibitor 2g highlight hydrophobic interactions with VAL126, PHE143, VAL520 and LYS526 and a halogen bond between the chlorine atom and ARG182.

In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone-carboxamide compounds 3h and 3s , which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC 50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity ( 3g : IC 50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e : IC 50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode., Competing Interests: The authors declare no conflicts of interest.

2′-hydroxy-chalcones are naturally occurring compounds with a wide array of bioactivity. In an effort to delineate the structural features that favor antioxidant and lipoxygenase (LOX) inhibitory activity, the design, synthesis, and bioactivity profile of a series of 2′-hydroxy-chalcones bearing diverse substituents on rings A and B, are presented. Among all the synthesized derivatives, chalcone 4b, bearing two hydroxyl substituents on ring B, was found to possess the best combined activity (82.4% DPPH radical scavenging ability, 82.3% inhibition of lipid peroxidation, and satisfactory LOX inhibition value (IC50 = 70 μM). Chalcone 3c, possessing a methoxymethylene substituent on ring A, and three methoxy groups on ring B, exhibited the most promising LOX inhibitory activity (IC50 = 45 μM). A combination of in silico techniques were utilized in an effort to explore the crucial binding characteristics of the most active compound 3c and its analogue 3b, to LOX. A common H-bond interaction pattern, orienting the hydroxyl and carbonyl groups of the aromatic ring A towards Asp768 and Asn128, respectively, was observed. Regarding the analogue 3c, the bulky (-OMOM) group does not seem to participate in a direct binding, but it induces an orientation capable to form H-bonds between the methoxy groups of the aromatic ring B with Trp130 and Gly247.

In this study, a range of oxamide ligands were synthesized by the reaction of amines with oxalyl chloride in basic medium. Spectroscopic and analytical techniques such as IR, 1H-NMR and ESI-MS techniques were used for characterization of the synthesized oxamides. The synthesized oxamides were screened for Lipoxygenase inhibition. Biological screening revealed that the oxamides possessed good lipoxygenase inhibition activities, whereas, the unsubstituted oxamide did not show any distinct lipoxygenase inhibition activity. Molecular docking studies of the oxamides were also carried out for lipoxygenase inhibition. The results obtained from molecular docking were well correlated with the empirical data. [ABSTRACT FROM AUTHOR]

Synthesis of new antioxidants and enzyme inhibitors is an active area of research in pharmaceutical sciences. This can be used for development of new active product ingredients which can prevent body from different diseases. This study comprises of preparation of transition metal complexes using 4-(4-bromophenyl)-2,2'-bipyridine (BPBP) and their screening for antioxidant and lipoxygenase inhibition properties. 4-(4-bromophenyl)-[2,2'-bipyridine]-6-carboxylic acid was used as starting material and its decarboxylation resulted in BPBP. Decarboxylation by conventional heating method was compared with microwave decarboxylation method. Selected metal complexes of the ligand were synthesized with Ruthenium (II), Iron (II) and Cobalt (II) ions. The complexes were characterized using UV, IR, 1HNMR, ESI-MS and CHNS techniques. It was observed that BPBP acted as a bidentate ligand. The metal to ligand stoichiometry was 1:3 for all the synthesized complexes. The complexes had octahedral structure with C3 symmetry. The antioxidant activity was evaluated using free radical scavenging assay. BPBP showed insignificant antioxidant and lipoxygenase activities while its transition metal complexes showed promising activities. Antioxidant activity of Fe and Co-complexes was found significantly higher than the reference drug used in this study. [ABSTRACT FROM AUTHOR]

Stratiotes aloides L. is common water plant in central Poland. Due to its expansive character, S. aloides L. can strongly affect the functioning of aquatic ecosystems. S. aloides L. was an important famine plant in central Poland. This plant was commonly collected and cooked until the turn of the 20th century. It has also been used to heal wounds, especially when these are made by an iron implement. The objective of the present work was to study the phenolic profile in the leaves and roots of S. aloides as well as their antioxidant potential and ability to inhibit lipoxygenase (LOX) in the light of their potential bioaccessibility. The dominant compound in its leaves was luteolin-7-O-hexoside-glucuronide (5.84 mg/g DW), whereas the dominant root component was chrysoeriol-7-O-hexoside-glucuronide (0.83 mg/g DW). Infusions from leaves, roots, and their 1:1 (v/v) mixture contained potentially bioaccessible antiradical compounds. S. aloides is a good source of water-extractable reductive compounds. Especially valuable are the leaves of this plant. The roots of S. aloides contained very active hydrophilic compounds able to chelate metal ions. However, their potential bioaccessibility was relatively low. The hydrophilic compounds from the leaves were the most effective XO inhibitors (EC50 = 9.91 mg DW/mL). The water-extractable compounds derived from the leaves and roots acted as uncompetitive LOX inhibitors.

The white beetroot cv. Śnieżna Kula is the first betanin-free beetroot registered in the European Union. The aim of this study was to compare the phenolic acids profile and antioxidant capacity of leaves of white (SK) and red (CC) beetroots and red (LC) and white (BL) Swiss chard growing in Poland. LC leaves were the richest source of total phenolics (16.55 mg GAE/g FW) and phenolic acids (1.81 mg/g FW), while the highest content of flavonoids was determined in CC leaves (1.6 mg QE/g FW). The highest antiradical activity was observed for LC, whereas CC extract exhibited the highest chelating power. BL and CC leaf extracts demonstrated high LOX inhibitory potential (EC50 = 53.23 and 56.97 mg FW/mL, respectively). An uncompetitive type of LOX inhibition was obtained for all extracts. SK extracts demonstrated the highest XO inhibitory activity (EC50 = 81.04 mg FW/mL). A noncompetitive type of XO inhibition was obtained in both extracts from red leaves (CC and LC), whereas an uncompetitive mode of inhibition was observed in the case of white leaf (SK and LC) extracts. Thus, it can be assumed that the presence of betanin influences the XO inhibition mechanism.

The five membered heterocyclic oxazole group plays an important role in drug discovery. Oxazolones present a wide range of biological activities. In this article the synthesis of 4-substituted-2-phenyloxazol-5(4H)-ones from the appropriate substituted aldehydes via an Erlenmeyer–Plochl reaction is reported. Subsequently, the corresponding benzamides were produced via a nucleophilic attack of a secondary amine on the oxazolone ring applying microwave irradiation. The compounds are obtained in good yields up to 94% and their structures were confirmed using IR, 1H-NMR, 13C-NMR and LC/MS data. The in vitro anti-lipid peroxidation activity and inhibitory activity against lipoxygenase and trypsin induced proteolysis of the novel derivatives were studied. Inhibition of carrageenin-induced paw edema (CPE) and nociception was also determined for compounds 4a and 4c. Oxazolones 2a and 2c strongly inhibit lipid peroxidation, followed by oxazolones 2b and 2d with an average inhibition of 86.5%. The most potent lipoxygenase inhibitor was the bisbenzamide derivative 4c, with IC50 41 μM. The benzamides 3c, 4a–4e and 5c were strong inhibitors of proteolysis. The replacement of the thienyl moiety by a phenyl group does not favor the protection. Compound 4c inhibited nociception higher than 4a. The replacement of thienyl groups by phenyl ring led to reduced biological activity. Docking studies of the most potent LOX inhibitor highlight interactions through allosteric mechanism. All the potent derivatives present good oral bioavailability.

Ethnopharmacological relevance Dilodendron bipinnatum Radlk., Sapindaceae, a tree of the Mato Grosso Pantanal , is popularly known as “mulher-pobre”. The decoction or infusion of its inner stem bark is used for treating inflammatory conditions. Aim of the study To determine if a 70% hydroethanolic extract of Dilodendron bipinnatum stem bark (HEDb) is able to reduce allergic airway inflammation in a murine model of ovalbumin (OVA)-induced allergic asthma. Material and methods The inner stem bark powder was macerated in a 70% hydroethanolic solution (1:3 w/v) to obtain HEDb. The induction of experimental asthma was accomplished as follows: on days 1 and 10, Swiss mice were sensitized by an intraperitoneal injection of OVA (100 µg/mL) and aluminum hydroxide (10 µg/mL). From day 19 to 24, animals (n = 6/per group) were treated (p.o.) twice a day with either vehicle (distilled water), HEDb (20, 100 and 500 mg/kg) or dexamethasone (0.5 mg/kg). Sham group animals were intraperitoneally injected and challenged with saline solution (0.9%) instead of OVA and received distilled water orally instead of HEDb, whereas the other groups were challenged with OVA (3% in saline) by aerosolization. On day 25, bronchoalveolar lavage fluid (BALF) was collected for the quantification of total leukocytes, neutrophils, eosinophils, mononuclear cells and Th2 cytokines (IL-4, IL-5, and IL-13). The lungs were collected for histopathological analysis and blood was assayed to determine serum IgE levels. The anti-inflammatory activity of HEDb was additionally confirmed by a lipoxygenase (LO) inhibitory assay in vitro. Results Compared to the sham group, the OVA group showed significantly greater numbers of total leukocytes, neutrophils, eosinophils, and mononuclear cells, as well as inflammatory cytokines in BALF, and also IgE in the serum. HEDb treated mice showed a significant decrease in inflammatory cell accumulation in BALF, with the maximum response observed at 500 mg/kg. Furthermore, the levels of IL-4, IL-5 and IL-13 in BALF, and of IgE in serum, were also considerably reduced as compared to the OVA group. The histopathological examination of the lungs of mice in the vehicle group showed a significant increase in hemorrhagic damage, mucus, perivascular and peribronchial inflammatory cell infiltrates, as well as mast cell degranulation compared to sham. HEDb (100 and 500 mg/kg) remarkably decreased all these parameters, presenting at the highest dose an anti-inflammatory effect comparable to that of dexamethasone (0.5 mg/kg). HEDb also had notable direct anti-inflammatory properties demonstrated by the inhibition of 15-LO activity in vitro (IC 50 = 1.0–5.0 µg/mL). Conclusions These results somewhat agree on the popular use of the inner stem bark of D. bipinnatum as a treatment for allergic asthma. The HEDb exhibits significant anti-inflammatory activity in the OVA-induced mouse model of allergic asthma, possibly due to the down-regulation of the Th2 responses and LO inhibition, resulting in improvements in all analyzed inflammatory parameters. [ABSTRACT FROM AUTHOR]

Methyl gallate was purified, by lipoxygenase (LOX) inhibitory activity-guided method since its alleged anti-inflammatory property, from Bergenia ligulata (Wall), a plant used in the traditional, Ayurvedic system of medicine extensively. The LOX inhibitory property of methyl gallate was studied by enzyme kinetics, isothermal titration calorimetry and molecular docking followed by molecular simulation studies. The wet-laboratory experiments and in silico studies showed complete agreement, and promise of methyl gallate as a drug-lead molecular scaffold for anti-inflammatory therapy, based on LOX inhibition. The expressed work shows the need of nonactive site binding parameters to be considered while designing of inhibitors based on the specificities toward active sites of enzymes. [ABSTRACT FROM AUTHOR]

Bismuth(III) complexes of the formulae [BiCl 3 (MBZT) 2 ] ·H 2 O} ( 1 ), {[BiCl 2 (µ 2 -Cl)(MMI) 2 ] 2 ·(CH 3 ) 2 CO} ( 2 ), {[BiCl 3 (µ 2 -S-PYT)(PYT)] 2 } ( 3 ) {([BiCl 2 (MBZIM) 4 ] + )·2(Cl - )·(H 3 O + ) ·2H 2 O} ( 4 ) and [BiCl 3 (tHPMT) 3 ] ( 5 ) (where MBZT: 2-mercaptobenzothiazole, MMI: 2-mercapto-1-methylimidazole, PYT: 2-mercaptopyridine, MBZIM: 2-mercaptobenzimidazole, tHPMT: 2-mercapto-3,4,5,6-tetrahydro-pyrimidine) are reported. The compounds were characterized by spectroscopic techniques including FT-IR, FT-Raman, UV-Vis, 1 H-, 13 C-NMR spectroscopies, TG-DTA, e.a, molar conductivity and by single-crystal X-ray diffraction analysis. While 1 , 4 and 5 are mononuclear compounds, 2 and 3 are dinuclear complexes in which the two Bi 3+ ions are bridged through Cl - and SR groups respectively. Interestingly, 3 is the first example of dinuclear Bi 3+ complex containing two Bi-(μ-SR)-Bi bridges between the two metal centers formed by covalent bonds. Compounds 1–5 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma cervix (HeLa) and breast (MCF-7) cells. The toxicity of 1 – 5 was evaluated on normal human fetal lung fibroblast cells (MRC-5). The influence of 1 – 5 , on the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX) was determined experimentally. [ABSTRACT FROM AUTHOR]

Novel derivatives of some non steroidal anti-inflammatory drugs, as well as of the antioxidants α-lipoic acid, trolox and (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid with lorazepam were synthesised by a straightforward method at satisfactory to high yields (40%−93%). All the tested derivatives strongly decreased lipidemic indices in rat plasma after Triton induced hyperlipidaemia. They also reduced acute inflammation and a number of them demonstrated lipoxygenase inhibitory activity. Those compounds acquiring antioxidant moiety were inhibitors of lipid peroxidation and radical scavengers. Therefore, the synthesised compounds may add to the current knowledge about multifunctional agents acting against various disorders implicating inflammation, dyslipidaemia and oxidative stress.

Inflammation is a complex phenomenon that results as a healing response of organisms to different factors, exerting immune signaling, excessive free radical activity and tissue destruction. Lipoxygenases and their metabolites e.g., LTB4, are associated with allergy, cell differentiation and carcinogenesis. Lipoxygenase 12/15 has been characterized as a mucosal-specific inhibitor of IgA and a contributor to the development of allergic sensitization and airway inflammation. Development of drugs that interfere with the formation or effects of these metabolites would be important for the treatment of various diseases like asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer and blood vessel disorders. In this study we extended our previous research synthesizing a series of multi-target cinnamic acids from the corresponding aldehydes with suitable 4-OH/Br substituted phenyl acetic acid by Knoevenagel condensation. The final products 1i, 3i, 3ii, 4i, 6i, 6ii, and 7i were obtained in high yields (52⁻98%) Their structures were verified spectrometrically, while their experimentally lipophilicity was determined as RM values. The novel derivatives were evaluated for their antioxidant activity using DPPH, hydroxyl radical, superoxide anion and ABTS+•, anti-lipid peroxidation and soybean lipoxygenase inhibition assays. The compounds presented medium interaction with DPPH (30⁻48% at 100 µM). In contrast all the synthesized derivatives strongly scavenge OH radicals (72⁻100% at 100 µM), ABTS+• (24⁻83% at 100 µM) and presented remarkable inhibition (87⁻100% at 100 µM) in linoleic acid peroxidation (AAPH). The topological polar surface of the compounds seems to govern the superoxide anion scavenging activity. Molecular docking studies were carried out on cinnamic acid derivative 3i and found to be in accordance with experimental biological results. All acids presented interesting lipoxygenase inhibition (IC50 = 7.4⁻100 µM) with compound 3i being the most potent LOX inhibitor with IC50 = 7.4 µM combining antioxidant activities. The antioxidant results support the LOX inhibitory activities. The recorded in vitro results highlight compound 3i as a lead compound for the design of new potent lipoxygenase inhibitors for the treatment of asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer and blood vessel disorders.

• Synthesis of new N -alkyl/ N -aryl derivatives (6a-n) of 5-((p -tolyloxymethyl)−4H-1,3,4-oxadiazole-2-ylthio)propanamide. • The potent to excellent inhibitory potential of 6 g , 6i, 6j and 6f with soybean 15-LOX. • Characterization by FTIR, 1H-, 13C NMR spectroscopy, EI-MS and HR-EI-MS spectrometry. • The ADME properties, molecular docking studies and DFT supported the in vitro findings. In humans, tissue injury result in the production of an inflammatory response and arachidonic acid released from the damaged membrane phospholipids is oxidized in two separate pathways, that is, lipoxygenase (LOX) and cyclooxygenase (COX) pathways, resulting in the production of biologically active mediators. The present work deals with the synthesis of a series of new N -alkyl/ N -aryl derivatives (6a-n) of 5-((p -tolyloxymethyl)-4H-1,3,4-oxadiazole-2-ylthio)propanamide and these analogues (6a-n) were characterized by modern spectroscopic and spectrometric techniques and scanned for their inhibition for soybean 15-LOX enzyme. The results showed the derivatives 6g, 6i and 6j as potent enzyme inhibitors with an IC 50 values 8.5 ± 0.4 µM, 11.4 ± 0.6 µM and 19.7 ± 0.4 µM. Compounds 6g and 6i maintained blood mononuclear cells (MNCs) viability of 75.5 ± 1.4%, 95.6 ± 1.5%, but 6j was found toxic with viability of 32.6 ± 1.6%, respectively, as determined by MTT assay. Rest of the compounds displayed good to poor inhibitory profiles against the said enzyme with IC 50 values from 24.6 ± 0.6 µM to 83.5 ± 0.5 µM which were also found nontoxic to MNCs under assay conditions except 6k which revealed only 23.6 ± 1.3% cellular viability. Calculated ADME properties predicted 'drug-like properties' of all compounds with good oral bioavailability profiles. Molecular docking studies showed that Lys526 and Trp772 in 6g established hydrogen bonding with the protein and π -alkyl (Val126, Val520, Pro530) and alkyl interaction (Arg533) further helped the ligand protein binding as depicted in quercetin where hydrogen bonding and π -alkyl interaction was recognized. In summary, the derivatives 6g and 6i demonstrated highly appreciable drug-like properties and warrant further investigations in search for potential leads as anti-LOX agents. Synthesis is a form of art that gathers a huge number of critical combinations of compounds having therapeutic and agrochemical effects. The compounds containing 1,3,4-oxadiazole ring shown interesting biological activities. Present work deals with the synthesis of fourteen oxadiazolepropanamides (6a-n) using cheapest raw ingredients and best yielding procedures. These derivatives were characterized by FTIR and NMR spectroscopic and EI-MS and HR-EI-MS spectrometric techniques. Both in vitro (15-Lipoxygenase inhibition, cytotoxicity) and in silico studies were conducted and remarkable results valued the current research work. [Display omitted] [ABSTRACT FROM AUTHOR]

The study investigated the anti-inflammatory activity of the hydro methanolic extract of six leafy vegetables, namely Cassia auriculata, Passiflora edulis, Sesbania grandiflora, Olax zeylanica, Gymnema lactiferum, and Centella asiatica. The anti-inflammatory activity of methanolic extracts of leafy vegetables was evaluated using four in vitro-based assays: hemolysis inhibition, proteinase inhibition, protein denaturation inhibition, and lipoxygenase inhibition. Results showed that the percent inhibition of hemolysis from these leaf extracts (25⁻100 µg/mL dry weight basis (DW)) was within the range from 5.4% to 14.9%, and the leaves of P. edulis and O. zeylanica showed a significantly higher (p < 0.05) inhibition levels. Percent inhibition of protein denaturation of these leafy types was within the range of 36.0⁻61.0%, and the leaf extract of C. auriculata has exhibited a significantly higher (p < 0.05) inhibition level. Proteinase inhibitory activity of these leaf extracts was within the range of 20.2⁻25.9%. The lipoxygenase inhibition was within the range of 3.7⁻36.0%, and the leaf extract of G. lactiferum showed an improved ability to inhibit lipoxygenase activity. In conclusion, results revealed that all the studied leaves possess anti-inflammatory properties at different levels, and this could be due to the differences in the composition and concentration of bioactive compounds.

[Display omitted] • Synthesis of new N -alkyl/aralky/aryl oxadiazole derivatives (6a-o) of 5-((p -tolyloxymethyl)-4H-1,3,4-oxadiazole-2-ylthio)acetamide. • The potent to excellent inhibitory potential of 6o, 6b, 6n and 6e with soybean 15-LOX. • Characterization by 1H-, 13C NMR spectroscopy, EI-MS and HR-EI-MS spectrometry. • Cellular viability suggested that most of the active compounds by MTT assay. • The ADME, molecular docking studies and DFT supported the in vitro findings. The underlying correlation between the inflammation, innate immunity and cancer is extensively familiar and linked through a process mediated by three enzymes; cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP 450). The ever increase in the reported side effects of the antiinflammatory drugs against the targeted enzymes and the resistance developed afterwards compels the researchers to synthesize new effective molecules with safer profile. On the basis of these facts, our ongoing research on 1,3,4-oxadiazole derivatives deals with the synthesis of a new series of N -alkyl/aralky/aryl derivatives of 5-((p -tolyloxymethyl)-4H-1,3,4-oxadiazole-2-ylthio)acetamide (6a-o) which were developed by the sequential conversion of p -tolyloxyacetic acid (a) into ester (1) hydrazide (2) and 5-(p -tolyloxymethyl)-4H-1,3,4-oxadiazole-2-thiol (3). The designed compounds (6a-o) were acquired by the reaction of 1,3,4-oxadiazole (3) with numerous electrophiles (5a-o) in KOH. The synthesized analogues (6a-o) were characterized by FTIR, 1H-, 13C NMR spectroscopy, EI-MS and HR-EI-MS spectrometry, and were further assessed for their inhibitory potential against the soybean 15-LOX enzyme. The results showed excellent inhibitory potential of the compounds against the said enzyme, specifically 6o, 6b, 6n and 6e with inhibitory values (IC 50 ± SEM) of 21.5 ± 0.76, 24.3 ± 0.45, 29.1 ± 0.65 and 31.3 ± 0.78 µM, respectively. These compounds displayed < 55 % blood mononuclear cells (MNCs) cellular viability as measured by MTT assay at 0.25 mM concentration. Other compounds demonstrated moderate inhibitory activities with IC 50 values in the range of 33.2 ± 0.78 to 96.3 ± 0.73 µM and exhibited little cellular viability against MNCs except 6i , 6j , 6 m and 6 k that showed 61–79 % cellular viability. It was observed that most of the compounds (6o, 6b, 6n, 6e) were found more toxic towards MNCs at studied concentration of 0.25 mM. SAR studies revealed that the positions and nature of substituents accompanying phenyl ring have great influence on 15-LOX inhibitory activity. In the most active compound 6o , the amino acids Asp768 and Val126 were involved in hydrogen bonding, Thr529 was linked with π -anion interaction and π -sulphur interaction was displayed with Tyr525 and two π -alkyl interactions were formed with the benzene ring and amino acid residues Pro530 and Arg533. The in silico pharmacokinetics profiles and density functional theory calculations of the compounds further supported the in vitro findings. Further work on the synthesis of more oxadiazole derivatives is in progress in search for potential 'leads' for the drug discovery as LOX inhibitors. [ABSTRACT FROM AUTHOR]

Two new sphingolipids: oxyacanthin A [(2S,3S,4R)-2-{[(2R,5E)-2-hydroxyoctadec-5-enoyl]amino}hexaeicosane-1,3,4-triol; 1] and B [(2S,3S,4R)-2-{[(2R,5E)-2-hydroxyoctadec-5-enoyl]amino}hexaeicosane-1,3,4-triol-1-O-β-D-glucopyranoside; 2], together with 1-octacosanol, β-sitosterol, β-sitosterol 3-O-β-D-glucopyranoside and luteolin 7-O-β-glucopyranoside were isolated from the methanolic extract of the whole plant of Carthamus oxyacantha. Their structures were elucidated using 1H and 13C NMR spectra and 2D NMR analyses (HMQC, HMBC and COSY) in combination with mass spectrometry (EI-MS, HR-EI-MS, FAB-MS and HR-FAB-MS) experiments and in comparison with the literature data of the related compounds. Both the compounds 1 and 2 showed inhibitory potential against lipoxygenase (LOX) in a concentration-dependent manner with IC50 values 83.3 ± 1.3 and 245.7 ± 1.1 µM, whereas compound 2 showed inhibition against enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values 65.3 ± 0.1 and 93.6 ± 0.1 µM, respectively. [ABSTRACT FROM AUTHOR]

Enzyme inhibition is a significant part of research in pharmaceutical field in view of the fact that these studies have directed to the innovations of drugs having remarkable performance in diverse physiological conditions. The present study was aimed to assess urease and lipoxygenase inhibitory activity of weight reducing tablets. For evaluating the urease activity indophenol method was employed using Thiourea as the model urease inhibitor. The lipoxygenase inhibition was evaluated by measuring the hydroperoxides produced in lipoxygenation reaction using a purified lipoxygenase with lionoleic acid as substrate. When formulation of the weight reducing tablets was compared at various concentrations (50, 100 and 500pg/ml). The antiurease activity and lipoxygenase inhibition activity increased in a dose dependent manner. The formulations under test have an excellent antiurease and lipoxygenase inhibition potential and prospective to be used in the cure of a variety of complications associated with the production of urease and lipoxygenase enzymes. [ABSTRACT FROM AUTHOR]

The antioxidant, lipoxygenase inhibitory activities and free radical scavenging capacity of the crude extract, aqueous and some organic fractions of dry and ripe fruit of Aegle marmelos. L were studied to understand the protective and therapeutic role for the use of the fruit as a remedy in different ailments. All the tested fractions and extracts showed to possess significant antioxidant, free radical scavenging capacity and lipoxygenase inhibitory potential. However, chloroform and aqueous fractions showed significant ability to quench radicals, to reduce ferric chloride and to inhibit soyabean lipoxygenase. Their antioxidant and lipoxygenase inhibition was estimated by IC50 values, for antioxidant ranging from 88-65% activity at concentration of 5-0.15μg/mL and similarly for lipoxygenase inhibition ranging from 89-69% at various concentrations of 5-0.15μg/mL, in chloroform and aqueous fractions respectively. The scavenger molecules in the dry and ripe fruit of A. marmelos may attribute to therapeutic and protective effect during different progressive stages of ailments. [ABSTRACT FROM AUTHOR]

Antiradical and lipoxygenase (LOX) inhibitory potential, mode of LOX inhibition and interactions between phytochemicals derived from coffee and dried coconut meat (DCM) in the light of their bioaccessibility in vitro were evaluated. LOX inhibitors and antiradical compounds from studied materials were bioaccessible in vitro. In the case of DCM simulated digestion caused a decrease of both activity (from 77.19 ± 0.02 to 86.21 ± 0.05 in case of LOX), which may be a consequence of low bioaccessibility and/or antagonistic interactions between active compounds, probably polyphenols. For better estimation of kind and strength of interaction the interaction factor (IF) was proposed. Water-extractable and potentially bioaccessible antiradical compounds from coffee and DCM acted synergistically (IF = 0.26). Water extractable LOX inhibitors acted antagonistically (IF = 1.12) and it was deepened after simulated digestion (IF = 1.51). Water-extractable phytochemicals from coffee acted as acompetitive, while potentially bioaccessible phytochemicals acted as noncompetitive LOX inhibitors. Water-extractable compounds from DCM acted as competitive whereas potentially bioaccessible fraction as noncompetitive inhibitors of LOX. Interestingly, water extractable and potentially bioaccessible compounds from coffee/DCM mixture did not change the maximum velocity of LOX (acted as competitive inhibitors). [ABSTRACT FROM AUTHOR]

Chemical investigations on the aerial parts ofCarissa opacaresulted in the isolation and characterization of two newnor-triterpenoids (compounds1and2) and a new sphingolipid (compound3) together with six known compounds. The structures of all the isolates were established using spectral data. All the isolated compounds showed DPPH radical scavenging and enzyme inhibitory activities against enzymes acetylcholinesterase, butyrylcholinesterase, and lipoxygenase. [ABSTRACT FROM AUTHOR]