Promising inhibition of diabetes-related enzymes and antioxidant properties of Ptilostemon casabonae leaves extract.

Type 2 diabetes (T2D) is a progressive metabolic disorder of glucose metabolism. One of the therapeutic approaches for the treatment of T2D is reducing postprandial hyperglycaemia through inhibition of the digestive enzymes α-glucosidase and α-amylase. In this context, aimed at identifying natural products endowed with anti-T2D potential, we focused on Ptilostemon casabonae (L.) Greuter, a species belonging to Asteraceae family. Enzymatic inhibition, antioxidant activity, phenolic composition and cellular assays were performed. This study revealed that the P. casabonae hydroalcoholic extract exerts a potent inhibitory activity against α-glucosidase. This activity is supported by an antioxidant effect, preventing ROS formation in a stressed cellular system. HPLC-PDA-MS/MS analysis, revealed a complex polyphenolic fraction. Among the tested pure compounds, 1,5-dicaffeoylquinic acid, apigenin and rutin displayed good α-glucosidase inhibitory activity. Our study suggested new potential of P. casabonae encouraging us to further testing the possible therapeutic potential of this extract.

Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application.

Introduction: Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to perform in vitro screening of natural and natural-like phenol monomers and their C2-symmetric dimers (hydroxylated biphenyls) in order to identify those representatives whose pharmacophores have the strongest antioxidant and the lowest prooxidant activity. Material and methods: Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated in vitro. Different (red/ox) assays were used to measure their total oxidative potential (TOP), their total antioxidative capacity (TAC), the pro-oxidative-antioxidant balance (PAB) and total SH-group content (SHG) in a biologically relevant environment. The Pro-oxidative Score, Antioxidative Score and the Oxy Score were also calculated. Trolox, a water soluble analogue of α-tocopherol, was used as a positive control. Results: In an assay consisting of pooled human serum, 6 of the 36 compounds showed significant antioxidant activity (compounds 6, 7, 12, 13, 26, and 27), whereas 4 showed extremely weak antioxidant activity (compounds 2, 29, 30, and 31). Within the 36 compounds comprising zingerone, dehydrozingerone, aurone, chalcone, and magnolol derivatives, in both monomeric and dimeric forms, the 2 compounds that indicated the highest antioxidant activity were dehydrozingerone derivatives (compounds 6 and 12). Trolox's activity was found between the strong and weak antioxidant compounds analysed in our study. Conclusions: In this study selected dehydrozingerones were identified as good candidates for in-depth testing of their biological behaviour and for possible precursors for synthesis of novel polyphenolic molecules with potential therapeutic applications.

Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls.

A comparative in vitro study of the antioxidant potential of natural phenols (zingerone, curcumin, raspberry ketone, magnolol) and their synthesized derivatives was performed. The antioxidant efficiency was evaluated in blood serum obtained from healthy individuals, by means of spectrophotometry, before and after the addition of pro-oxidant tert-butyl hydroperoxide (TBH). Moreover, the antioxidant effect of an equimolar mixture of curcumin and zingerone was investigated. Interpretation of our results reveals that in the blood serum of healthy individuals curcumin (C1), raspberry ketone (RK1), magnolol (M1) and synthesized derivative of zingerone (Z2) demonstrate remarkable antioxidant effects (p < 0.05). However, in the state of TBH-induced excessive oxidative stress natural magnolol and synthesized derivatives C1, Z1 and RK1 show powerful antioxidant activity and thus can be further investigated to obtain information about their metabolic transformations and their potential influence at the cellular level. Results obtained from measurements in an equimolar mixture of zingerone and curcumin indicate synergism (p < 0.05) between the two compounds. This combination is especially successful due to the fast and efficient neutralization of added pro-oxidant TBH. The commercial availability of turmeric and ginger and their frequent combined use in diet suggest ideas for further broader utilization of the beneficial synergistic effect of their phenolic components.

Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis.

Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 µM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 µM, and by amperometric assay with IC50 for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 µM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein.

Antamanide Analogs as Potential Inhibitors of Tyrosinase.

The tyrosinase enzyme, which catalyzes the hydroxylation of monophenols and the oxidation of o-diphenols, is typically involved in the synthesis of the dark product melanin starting from the amino acid tyrosine. Contributing to the browning of plant and fruit tissues and to the hyperpigmentation of the skin, leading to melasma or age spots, the research of possible tyrosinase inhibitors has attracted much interest in agri-food, cosmetic, and medicinal industries. In this study, we analyzed the capability of antamanide, a mushroom bioactive cyclic decapeptide, and some of its glycine derivatives, compared to that of pseudostellarin A, a known tyrosinase inhibitor, to hinder tyrosinase activity by using a spectrophotometric method. Additionally, computational docking studies were performed in order to elucidate the interactions occurring with the tyrosinase catalytic site. Our results show that antamanide did not exert any inhibitory activity. On the contrary, the three glycine derivatives AG9, AG6, and AOG9, which differ from each other by the position of a glycine that substitutes phenylalanine in the parent molecule, improving water solubility and flexibility, showed tyrosinase inhibition by spectrophotometric assays. Analytical data were confirmed by computational studies.

Biopolymer: A Sustainable Material for Food and Medical Applications.

Biopolymers are a leading class of functional material suitable for high-value applications and are of great interest to researchers and professionals across various disciplines. Interdisciplinary research is important to understand the basic and applied aspects of biopolymers to address several complex problems associated with good health and well-being. To reduce the environmental impact and dependence on fossil fuels, a lot of effort has gone into replacing synthetic polymers with biodegradable materials, especially those derived from natural resources. In this regard, many types of natural or biopolymers have been developed to meet the needs of ever-expanding applications. These biopolymers are currently used in food applications and are expanding their use in the pharmaceutical and medical industries due to their unique properties. This review focuses on the various uses of biopolymers in the food and medical industry and provides a future outlook for the biopolymer industry.

Structural Insight of New Butyrylcholinesterase Inhibitors Based on Benzylbenzofuran Scaffold.

In the present work, we use a merger of computational and biochemical techniques as a rational guideline for structural modification of benzofuran derivatives to find pertinent structural features for the butyrylcholinesterase inhibitory activity and selectivity. Previously, we revealed a series of 2-phenylbenzofuran compounds that displayed a selective inhibitory activity for BChE. Here, in an effort to discover novel selective BChE inhibitors with favorable physicochemical and pharmacokinetic profiles, 2-benzylbenzofurans were designed, synthesized, and evaluated as BChE inhibitors. The 2-phenylbenzofuran scaffold structure is modified by introducing one methylene spacer between the benzofuran core and the 2-phenyl ring with a hydroxyl substituent in the para or meta position. Either position 5 or 7 of the benzofuran scaffold was substituted with a bromine or chlorine atom. Further assessment of the selected list of compounds indicated that the substituent's nature and position determined their activity and selectivity. 5-bromo-2-(4-hydroxybenzyl)benzofuran 9B proved to be the most potent butyrylcholinesterase inhibitor (IC50 = 2.93 µM) of the studied series. Computational studies were carried out to correlate the theoretical and experimental binding affinity of the compounds to the BChE protein.

Bioprospecting Phenols as Inhibitors of Trichothecene-Producing Fusarium: Sustainable Approaches to the Management of Wheat Pathogens.

Fusarium spp. are ubiquitous fungi able to cause Fusarium head blight and Fusarium foot and root rot on wheat. Among relevant pathogenic species, Fusarium graminearum and Fusarium culmorum cause significant yield and quality loss and result in contamination of the grain with mycotoxins, mainly type B trichothecenes, which are a major health concern for humans and animals. Phenolic compounds of natural origin are being increasingly explored as fungicides on those pathogens. This review summarizes recent research activities related to the antifungal and anti-mycotoxigenic activity of natural phenolic compounds against Fusarium, including studies into the mechanisms of action of major exogenous phenolic inhibitors, their structure-activity interaction, and the combined effect of these compounds with other natural products or with conventional fungicides in mycotoxin modulation. The role of high-throughput analysis tools to decipher key signaling molecules able to modulate the production of mycotoxins and the development of sustainable formulations enhancing potential inhibitors' efficacy are also discussed.

Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin.

Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (endo coumarin-resveratrol-inspired hybrid) and trans-6-styrylcoumarin (exo coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with trans-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than trans-resveratrol.

Molecular Docking and Comparative Inhibitory Efficacy of Naturally Occurring Compounds on Vegetative Growth and Deoxynivalenol Biosynthesis in Fusarium culmorum.

The fungal pathogen Fusarium culmorum causes Fusarium head blight in cereals, resulting in yield loss and contamination of the grain by type B trichothecene mycotoxins such as deoxynivalenol (DON), and its acetylated derivatives. Synthesis of trichothecenes is driven by a trichodiene synthase (TRI5) that converts farnesyl pyrophosphate (FPP) to trichodiene. In this work, 15 naturally occurring compounds that belong to the structural phenol and hydroxylated biphenyl classes were tested in vitro and in planta (durum wheat) to determine their inhibitory activity towards TRI5. In vitro analysis highlighted the fungicidal effect of these compounds when applied at 0.25 mM. Greenhouse assays showed a strong inhibitory activity of octyl gallate 5, honokiol 13 and the combination propyl gallate 4 + thymol 7 on trichothecene biosynthesis. Docking analyses were run on the 3D model of F. culmorum TRI5 containing the inorganic pyrophosphate (PPi) or FPP. Significant ligand affinities with TRI-PPi and TRI-FPP were observed for the same sites for almost all compounds, with 1 and 2 as privileged sites. Octyl gallate 5 and honokiol 13 interacted almost exclusively with sites 1 and 2, by concurrently activating strong H-bonds with common sets of amino acids. These results open new perspectives for the targeted search of naturally occurring compounds that may find practical application in the eco-friendly control of FHB in wheat.

Euphorbia characias: Phytochemistry and Biological Activities.

The aim of this review is to summarize all the compounds identified and characterized from Euphorbia characias, along with the biological activities reported for this plant. Euphorbia is one of the greatest genera in the spurge family of Euphorbiaceae and includes different kinds of plants characterized by the presence of milky latex. Among them, the species Euphorbia characias L. is an evergreen perennial shrub widely distributed in Mediterranean countries. E. characias latex and extracts from different parts of the plant have been extensively studied, leading to the identification of several chemical components such as terpenoids, sterol hydrocarbons, saturated and unsaturated fatty acids, cerebrosides and phenolic and carboxylic acids. The biological properties range between antioxidant activities, antimicrobial, antiviral and pesticidal activities, wound-healing properties, anti-aging and hypoglycemic properties and inhibitory activities toward target enzymes related to different diseases, such as cholinesterases and xanthine oxidase. The information available in this review allows us to consider the plant E. characias as a potential source of compounds for biomedical research.

Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells.

Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds-namely, compounds 11 and 12-were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 ± 0.5 µM for 11 and 2.0 ± 0.7 µM for 12) and no toxicity of normal fibroblasts up to 32 µM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed long-lasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.

GC/MSn analysis of the crude reaction mixtures from Friedel-Crafts acylation: Unambiguous identification and differentiation of 3-aroylbenzofurans from their 4- and 6-regioisomers.

RATIONALE: 3-Aroylbenzofurans and their 2-nitrophenyl derivatives constitute fundamental intermediates for the synthesis of target compounds with pharmaceutical properties. However, their preparation via the Friedel-Crafts acylation of 2-phenylbenzofurans, using Lewis acid as catalyst, often leads to mixtures of regioisomeric aroylbenzofurans that can be challenging to distinguish, thus preventing the reaction characterization. METHOD: We report a method for the unambiguous identification and differentiation of the desired 3-benzoyl isomers from their 4- and 6-regioisomers in a crude reaction mixture using gas chromatography coupled to multiple-stage mass spectrometric (GC/MSn ) analysis performed in collision-induced dissociation (CID) mode. RESULTS: Upon electron ionization, each set of isomers displayed nearly identical mass spectra. MSn revealed fragmentation patterns that varied in the location of the benzoyl group on the benzofuran scaffold: CID experiments performed on the molecular ion allowed the distinction of the 3-acyl isomers from the 4- and 6-regioisomers; CID experiments on the [M - Ar]+ ion allowed the distinction of the 4-benzoyl from the 6-benzoyl regioisomer, when the nitro group is located on the 2-phenyl ring. Moreover, the unusual loss of OH• radical allowed ascertaining the position of the nitro group in 3-acyl regioisomers bearing the NO2 group. The origin of the diagnostic OH• loss was investigated through MSn experiments using 18 O-labelled 3-benzoyl derivatives. CONCLUSIONS: The method allows the rapid characterization of crude reaction mixtures of benzoylbenzofurans using solely GC/MSn analysis, simplifying the workflow of extensive isolation and purification for structure elucidation.

Synthesis and in vitro study of nitro- and methoxy-2-phenylbenzofurans as human monoamine oxidase inhibitors.

A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran moiety determine the affinity for MAO-A or MAO-B. The 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 was the most potent MAO-B inhibitor (IC50 = 0.024 µM) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC50 = 0.168 µM), both acting as reversible inhibitors. The number and position of the methoxyl groups on the 2-phenyl ring, have an important influence on the inhibitory activity. Molecular docking studies confirmed the experimental results and highlighted the importance of key residues in enzyme inhibition.

Prenylated Trans-Cinnamic Esters and Ethers against Clinical Fusarium spp.: Repositioning of Natural Compounds in Antimicrobial Discovery.

Onychomycosis is a common nail infection mainly caused by species belonging to the F. oxysporum, F. solani, and F. fujikuroi species complexes. The aim of this study was to evaluate the in vitro susceptibility of six representative strains of clinically relevant Fusarium spp. toward a set of natural-occurring hydroxycinnamic acids and their derivatives with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. By introducing a prenylated chain at one of the hydroxy groups of trans-cinnamic acids 1-3, ten prenylated derivatives (coded 4-13) were preliminarily investigated in solid Fusarium minimal medium (FMM). Minimal inhibitory concentration (MIC) and lethal dose 50 (LD50) values were then determined in liquid FMM for the most active selected antifungal p-coumaric acid 3,3'-dimethyl allyl ester 13, in comparison with the conventional fungicides terbinafine (TRB) and amphotericin B (AmB), through the quantification of the fungal growth. Significant growth inhibition was observed for prenylated derivatives 4-13, evidencing ester 13 as the most active. This compound presented MIC and LD50 values (62-250 µM and 7.8-125 µM, respectively) comparable to those determined for TRB and AmB in the majority of the tested pathogenic strains. The position and size of the prenylated chain and the presence of a free phenol OH group appear crucial for the antifungal activity. This work represents the first report on the activity of prenylated cinnamic esters and ethers against clinical Fusarium spp. and opens new avenues in the development of alternative antifungal compounds based on a drug repositioning strategy.

Antioxidant properties of novel curcumin analogues: A combined experimental and computational study.

The multi-target activity of curcumin makes it a promising pharmacological lead for structural modifications focused on the preparation of new better therapeutics with improved bioavailability. A possible modification is to "decompose" the parent curcumin structure into constituent units and to build up curcumin analogues with biphenyl structural moiety. The antioxidant properties of the so-called "monomers" (m1-m3) and "dimers" (d1-d3) are studied experimentally and computationally. Their protective effects as chain-breaking antioxidants are investigated for the individual compounds and in binary/ternary compositions with α-tocopherol (TOH) and ascorbyl palmitate (AscPH). All monomers manifest significant synergism up to 70% in mixtures with TOH. Synergistic effects are found for the ternary compositions of monomeric analogues upon addition to the binary mixture of standard antioxidants (TOH + AscPH). Dimers with biphenyl skeleton manifest a lower potential in compositions under lipid oxidation conditions. DFT computations provide a detailed insight into the structure and antiradical properties of the curcumin analogues and standard antioxidants. PRACTICAL APPLICATIONS: Bioactive compounds in the diet play a crucial role in the prevention of numerous diseases in whose pathogenesis oxidative stress is well known to be involved. Therefore, enhancement of the antioxidant status of the biological target is often helpful. Two of the monomers studied are considered leading agents in the treatment or prophylaxis of smooth muscle disorders and are useful in the maintenance of the normal gut function- as a calmative for the gut and to ease upset stomach. We hypothesized that the presence of a biphenyl scaffold in the parent molecular structure can enhance the biological activity. Equimolar mixtures of TOH with studied compounds have potential application in food chemistry and medicine. A composition comprising the active agent and additional components (strong conventional antioxidants) may be administered in foodstuffs, as a food supplement, beverage supplement, or as a pharmaceutical composition.

A new biological prospective for the 2-phenylbenzofurans as inhibitors of α-glucosidase and of the islet amyloid polypeptide formation.

In this study, we have investigated a series of hydroxylated 2-phenylbenzofurans compounds for their inhibitory activity against α-amylase and α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes seem to have an important role as antidiabetic drugs. Diabetes mellitus is a wide-spread metabolic disease characterized by elevated levels of blood glucose. The most common is type 2 diabetes, which can lead to severe complications. Since the aggregates of islet amyloid polypeptide (IAPP) are common in diabetic patients, the effect of compounds to inhibit amyloid fibril formation was also determined. All the compounds assayed showed to be more active against α-glucosidase. Compound 16 showed the lowest IC50 value of the series, and it is found to be 167 times more active than acarbose, the reference compound. The enzymatic activity assays showed that compound 16 acts as a mixed-type inhibitor of α-glucosidase. Furthermore, compound 16 displayed effective inhibition of IAPP aggregation and it manifested no significant cytotoxicity. To predict the binding of compound 16 to IAPP and α-glucosidase protein complexes, molecular docking studies were performed. Altogether, our results support that the 2-phenylbenzofuran derivatives could represent a promising candidate for developing molecules able to modulate multiple targets involved in diabetes mellitus disorder.

Synthesis of Hydroxylated Biphenyl Derivatives Bearing an α,ß-Unsaturated Ketone as a Lead Structure for the Development of Drug Candidates against Malignant Melanoma.

A small collection of C2 -symmetric hydroxylated biphenyl derivatives featuring an α,ß-unsaturated ketone as a lead structure was prepared, and the capacity of these compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve the delivery of compounds into the cell by modulation of the phenolic hydroxy protecting group. The hydroxylated biphenyl structure bearing an α,ß-unsaturated ketone and a phenolic-O-prenylated chain was found to facilitate the delivery of the molecule and interactions with biological targets. Four compounds showed antiproliferative activity resulting in IC50 values in the range of 1.2 to 2.8 µM.

Naturally Occurring Phenols Modulate Vegetative Growth and Deoxynivalenol Biosynthesis in Fusarium graminearum.

To assess the in vitro activity of five naturally occurring phenolic compounds (ferulic acid, apocynin, magnolol, honokiol, and thymol) on mycelial growth and type B trichothecene mycotoxin accumulation by Fusarium graminearum, three complementary approaches were adopted. First, a high-throughput photometric continuous reading array allowed a parallel quantification of F. graminearum hyphal growth and reporter TRI5 gene expression directly on solid medium. Second, RT-qPCR confirmed the regulation of TRI5 expression by the tested compounds. Third, liquid chromatography-tandem mass spectrometry analysis allowed quantification of deoxynivalenol (DON) and its acetylated forms released upon treatment with the phenolic compounds. Altogether, the results confirmed the activity of thymol and an equimolar mixture of thymol-magnolol at 0.5 mM, respectively, in inhibiting DON production without affecting vegetative growth. The medium pH buffering capacity after 72-96 h of incubation is proposed as a further element to highlight compounds displaying trichothecene inhibitory capacity with no significant fungicidal effect.

Looking for new xanthine oxidase inhibitors: 3-Phenylcoumarins versus 2-phenylbenzofurans.

Overproduction of uric acid in the body leads to hyperuricemia, which is also closely related to gout. Uric acid production can be lowered by xanthine oxidase (XO) inhibitors. Inhibition of XO has also been proposed as a mechanism for improving cardiovascular health. Therefore, the search for new efficient XO inhibitors is an interesting topic in drug discovery. 3-Phenylcoumarins and 2-phenylbenzofurans are privileged scaffolds in medicinal chemistry. Their structural similarity makes them interesting molecules for a comparative study. Methoxy and nitro substituents were introduced in both scaffolds. The current study gives some insights into the synthesis and biological activity of these molecules against this important target. For the best compound of the series, the 3-(4-methoxyphenyl)-6-nitrocoumarin (4), the IC50 value, type of inhibition, cytotoxicity on B16F10 cells and ADME theoretical properties, were determined. Docking studies were also performed in order to better understand the interactions of this molecule with the XO binding pocket. This work is a preliminary screening for further design and synthesis of new non-purinergic derivatives as potential compounds involved in the inflammatory suppression, specially related to gout.