Anticancer Therapies Based on Oxidative Damage: Lycium barbarum Inhibits the Proliferation of MCF-7 Cells by Activating Pyroptosis through Endoplasmic Reticulum Stress.

Lycium barbarum, commonly recognized as goji berry or wolfberry, is highly appreciated not only for its organoleptic and nutritional properties but also as an important source of bioactive compounds such as polysaccharides, carotenoids, phenolics, and various other non-nutritive compounds. These constituents give it a multitude of health benefits, including antioxidant, anti-inflammatory, and anticancer properties. However, the precise biochemical mechanisms responsible for its anticancer effects remain unclear, and the comprehensive composition of goji berry extracts is often insufficiently explored. This study aimed to investigate the biochemical pathways modulated in breast cancer cells by an ethanolic extract of Lycium barbarum fruit (LBE). Following metabolomic profiling using UHPLC-HRMS/MS, we assessed the antitumoral properties of LBE on different breast cancer cell lines. This investigation revealed that LBE exhibited cytotoxic effects, inducing a pro-oxidant effect that triggered pyroptosis activation through endoplasmic reticulum (ER) stress and subsequent activation of the P-IRE1α/XBP1/NLRP3 axis in MCF-7 cells. In addition, LBE did not display cytotoxicity toward healthy human cells but demonstrated antioxidant properties by neutralizing ROS generated by doxorubicin. These findings underscore the potential of LBE as a highly promising natural extract in cancer therapy.

Antitumor Mechanisms of Lycium barbarum Fruit: An Overview of In Vitro and In Vivo Potential.

Lycium barbarum, known as goji berry or wolfberry, is a fruit long associated with health benefits, showing a plethora of effects ranging from antioxidant, anticancer, anti-inflammatory, and immunomodulatory effects. Its potential is attributed to the significant presence of polysaccharides, glycopeptides, polyphenols, flavonoids, carotenoids, and their derivatives. These compounds effectively counteract the action of free radicals, positively influencing cellular balance and intracellular signaling, contributing to overall cell health and function acting on multiple molecular pathways. Several fractions extracted from goji berries demonstrate antitumor properties, particularly effective against breast cancer, without showing cytotoxic effects on normal human cells. Hence, the review explored the fundamental traits of bioactive elements in Lycium barbarum and their potential in cancer treatment and, specifically, breast cancer. It focused on elucidating wolfberry's influenced biochemical pathways, its synergism with anticancer drugs, and its potential to alleviate the side effects associated with existing cancer treatments.

Peptidomimetics as potent dual SARS-CoV-2 cathepsin-L and main protease inhibitors: In silico design, synthesis and pharmacological characterization.

In this paper we present the design, synthesis, and biological evaluation of a new series of peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (MPro) and Papain Like Protease (PLPro) dual inhibitor, CV11, here we disclose its high inhibitory activity against cathepsin L (CTSL) (IC50 = 19.80 ± 4.44 nM), an emerging target in SARS-CoV-2 infection machinery. An in silico design, inspired by the structure of CV11, led to the development of a library of peptidomimetics showing interesting activities against CTSL and Mpro, allowing us to trace the chemical requirements for the binding to both enzymes. The screening in Vero cells infected with 5 different SARS-CoV-2 variants of concerns, highlighted sub-micromolar activities for most of the synthesized compounds (13, 15, 16, 17 and 31) in agreement with the enzymatic inhibition assays results. The compounds showed lack of activity against several different RNA viruses except for the 229E and OC43 human coronavirus strains, also characterized by a cathepsin-L dependent release into the host cells. The most promising derivatives were also evaluated for their chemical and metabolic in-vitro stability, with derivatives 15 and 17 showing a suitable profile for further preclinical characterization.

Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides.

In recent years, peptides have gained more success as therapeutic compounds. Nowadays, the preferred method to obtain peptides is solid-phase peptide synthesis (SPPS), which does not respect the principles of green chemistry due to the large number of toxic reagents and solvents used. The aim of this work was to research and study an environmentally sustainable solvent able to replace dimethylformamide (DMF) in fluorenyl methoxycarbonyl (Fmoc) solid-phase peptide synthesis. Herein, we report the use of dipropyleneglycol dimethylether (DMM), a well-known green solvent with low human toxicity following oral, inhalant, and dermal exposure and that is easily biodegradable. Some tests were needed to evaluate its applicability to all the steps of SPPS, such as amino acid solubility, resin swelling, deprotection kinetics, and coupling tests. Once the best green protocol was established, it was applied to the synthesis of different length peptides to study some of the fundamental parameters of green chemistry, such as PMI (process mass intensity) and the recycling of solvent. It was revealed that DMM is a valuable alternative to DMF in all steps of solid-phase peptide synthesis.

Potential Role of Natural Antioxidant Products in Oncological Diseases.

Nutrition has a significant effect and a crucial role in disease prevention. Low consumption of fruit and vegetables and a sedentary lifestyle are closely related with the onset and development of many types of cancer. Recently, nutraceuticals have gained much attention in cancer research due to their pleiotropic effects and relatively non-toxic behavior. In fact, although in the past there have been conflicting results on the role of some antioxidant compounds as allies against cancer, numerous recent clinical studies highlight the efficacy of dietary phytochemicals in the prevention and treatment of cancer. However, further investigation is necessary to gain a deeper understanding of the potential anticancer capacities of dietary phytochemicals as well as the mechanisms of their action. Therefore, this review examined the current literature on the key properties of the bioactive components present in the diet, such as carotenoids, polyphenols, and antioxidant compounds, as well as their use in cancer therapy. The review focused on potential chemopreventive properties, evaluating their synergistic effects with anticancer drugs and, consequently, the side effects associated with current cancer treatments.

Beyond Retigabine: Design, Synthesis, and Pharmacological Characterization of a Potent and Chemically Stable Neuronal Kv7 Channel Activator with Anticonvulsant Activity.

Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator clinically approved for seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon the recently described cryoEM structure of Kv7.2 complexed with retigabine and on previous structure-activity relationship studies, a small library of retigabine analogues has been designed, synthesized, and characterized for their Kv7 opening ability using both fluorescence- and electrophysiology-based assays. Among all tested compounds, 60 emerged as a potent and photochemically stable neuronal Kv7 channel activator. Compared to retigabine, compound 60 displayed a higher brain/plasma distribution ratio, a longer elimination half-life, and more potent and effective anticonvulsant effects in an acute seizure model in mice. Collectively, these data highlight compound 60 as a promising lead compound for the development of novel Kv7 activators for the treatment of hyperexcitability diseases.

Stereoselective Synthesis of Selenium-Containing Glycoconjugates via the Mitsunobu Reaction.

A simple and efficient route for the synthesis of new glycoconjugates has been developed. The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joined to a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontrol detected in the Mitsunobu key reaction led to the most attractive product showing a natural d-configuration. Thus, we were able to obtain the target molecules from the commercially available d-ribose via a shorter and convenient sequence of reactions.

Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies.

Abstract: The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ability to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells (H9c2), and human breast adenocarcinoma cell line (MCF-7) exposed to doxorubicin. Interestingly, we found that the mix resulting from Citrus sinensis and Vitis vinifera association in ratio 1:1 was able to reduce cardiomyocytes damage induced by anthracyclines, without significantly interfering with the pro-apoptotic activity of the drug on breast cancer cells. These results point out the potential use of vegetable smoothies as adjuvants functional foods for chemotherapeutic anticancer protocols.

An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia.

Cytarabine, the 4-amino-1-(ß-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.

Antitumor agents 7. Synthesis, antiproliferative activity and molecular modeling of new l-lysine-conjugated pyridophenoxazinones as potent DNA-binding ligands and topoisomerase IIα inhibitors.

A series of l-lysine-conjugated pyridophenoxazinones 2-5 and 2'-5' were designed and synthesized for developing compounds with multimodal anticancer potentialities. All compounds inhibited the proliferation of a panel of human liquid and solid neoplastic cell lines. 2 and 5 were the most active compounds with IC50 values in the submicromolar range. UV-vis, 1H NMR, unwinding, and docking experiments demonstrated that they intercalate between the middle 5'-GC-3' base pairs with the carboxamide side chain lying into major groove. Charge-transfer contribution to the complex stability, evaluated by ab initio calculations, was found to correlate with cytotoxicity. Relaxation and cleavage assays showed that 2 and 5 selectively target Topo IIα over Topo IIß and stimulate the formation of covalent Topo II-DNA complexes, functioning as poisons. Moreover, compound 5 induced DNA damage and arrested MCF-7 cells at the G2/M phase. Altogether, the work provides interesting structure-activity relationships in the pyridophenoxazinone-l-lysine conjugate series and identifies 5 as a promising candidate for further in vivo evaluation.

Synthesis and Pharmacological Characterization of Conformationally Restricted Retigabine Analogues as Novel Neuronal Kv7 Channel Activators.

Kv7 K+ channels represent attractive pharmacological targets for the treatment of different neurological disorders, including epilepsy. In this paper, 42 conformationally restricted analogues of the prototypical Kv7 activator retigabine have been synthesized and tested by electrophysiological patch-clamp experiments as Kv7 agonists. When compared to retigabine (0.93 ± 0.43 µM), the EC50s for Kv7.2 current enhancements by compound 23a (0.08 ± 0.04 µM) were lower, whereas no change in potency was observed for 24a (0.63 ± 0.07 µM). In addition, compared to retigabine, 23a and 24a showed also higher potency in activating heteromeric Kv7.2/Kv7.3 and homomeric Kv7.4 channels. Molecular modeling studies provided new insights into the chemical features required for optimal interaction at the binding site. Stability studies evidenced improved chemical stability of 23a and 24a in comparison with retigabine. Overall, the present results highlight that the N5-alkylamidoindole moiety provides a suitable pharmacophoric scaffold for the design of chemically stable, highly potent and selective Kv7 agonists.

Anti-Inflammatory and Antioxidant Properties of Dehydrated Potato-Derived Bioactive Compounds in Intestinal Cells.

Inflammation and oxidative stress are always more recognized as responsible for chronic disease at the intestinal level. Currently, a growing interest is addressed to the discovery of diet-derived products which have anti-inflammatory and antioxidant properties. This work aims to characterize the pharmacological potential of dehydrated potatoes. For this purpose, a simulated gastrointestinal digestion was carried out. The bioaccessible peptides were fractionated on the basis of their molecular weight and tested on intestinal epithelial cells (IEC-6) under oxidative and inflammatory conditions. Our results demonstrate that the tested peptide fractions were able to significantly inhibit tumor necrosis factor-α release and cycloxygenase-2 and inducible nitric oxide synthase expression. The tested peptides also showed significant antioxidant activity, being able to both reduce reactive oxygen species (ROS) release, also from mitochondria, and nitrotyrosine formation, and increase the antioxidant response by heme oxygenase-1 and superoxide dismutase expression. Moreover, the peptide fractions were able to significantly increase the wound repair in IEC-6. The obtained results indicate the anti-inflammatory and antioxidant potential of dehydrated potatoes at the intestinal level.

Online comprehensive hydrophilic interaction chromatography × reversed phase liquid chromatography coupled to mass spectrometry for in depth peptidomic profile of microalgae gastro-intestinal digests.

In this study, a comprehensive hydrophilic interaction chromatography × reversed phase coupled to high resolution mass spectrometry was developed for the peptide profile of microalgae formulations subjected to gastro-intestinal digestion. A BEH Amide column was employed in the first dimension, while a BIOshell ES-C18 Peptide in the second. As modulation interface, two trapping columns, in house packed with 1.9 µm fully porous monodisperse C18 particles characterized by high retention and efficiency, were tested and compared with SecurityGuard C18 cartridges, together with a dilution flow, to reduce first dimension mobile phase strength. The platform was coupled to both diode array detector and Orbitrap mass spectrometry. The developed setup provided high peak capacity (nc: 957) in only 60 min and a good orthogonality (A0: 0.70). The employment of the custom made C18 traps resulted in improved sensitivity (signal enhancement = 4) and a higher number of peptides detected (+58) especially of short lenght (≤ 6 aminoacids), with respect to the setup based on the security guard C18 traps. 184 phycocyanin-derived peptides were detected in Klamath and Spirulina gastro-intestinal digests, whose sequence and protein origin has been elucidated in detail by mass spectrometry. The results show the potential of the developed HILIC × RP-MS platform for in depth peptide mapping of microalgae and its possible application to highlight the products of gastro-intestinal digestion of other microalgae species.

Yield parameters and antioxidant compounds of tomato fruit: the role of plant defence inducers with or without Cucumber mosaic virus infection.

BACKGROUND: The production of fruit and vegetables rich in health-promoting components in an eco-friendly context represents the winning answer to the world population demand for food. In this study, the effects of different treatments on the yield and fruit chemical characteristics of tomato (Solanum lycopersicum L.) are reported. The treatments included three inducers of plant defence responses (chitosan, Trichoderma harzianum T-22 and Bacillus subtilis QST713) applied alone or before Cucumber mosaic virus infection. Fruit production and antioxidant compounds were investigated by ultrahigh-performance liquid chromatography (UHPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Compared to control fruit harvested from untreated and healthy plants, treatment with QST713 increased the fruit number. Furthermore, plant treatments with T22, QST713 and chitosan alone enhanced fruit carotenoids (lutein and ß-carotene), ascorbic acid and phenolic acids (caffeoyl glucoside and p-coumaroyl glucoside). In parallel, compared to fruit harvested from only CMV-infected plants, treatments with T22, QST713 and chitosan before CMV enhanced fruit ascorbic acid and flavonoids (quercetin 3-O-xylosyl-rutinoside and rutin). CONCLUSION: Antioxidant compounds of tomato fruit can increase with the application of the plant defence inducers, thus protecting both the consumer and plant health. © 2019 Society of Chemical Industry.

Polyphenolic Extract from Tarocco (Citrus sinensis L. Osbeck) Clone "Lempso" Exerts Anti-Inflammatory and Antioxidant Effects via NF-kB and Nrf-2 Activation in Murine Macrophages.

Citrus fruits are often employed as ingredients for functional drinks. Among Citrus, the variety, "Lempso", a typical hybrid of the Calabria region (Southern Italy), has been reported to possess superior antioxidant activity when compared to other common Citrus varieties. For these reasons, the aim of this study is to investigate in vitro the nutraceutical value of the Tarocco clone, "Lempso", highlighting its anti-inflammatory and antioxidant potential. A post-column 2,2'-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging assay for the screening of antioxidant compounds in these complex matrices was developed. Subsequently, polyphenolic extract was tested on a murine macrophage cell line under inflammatory conditions. The extract resulted was able to significantly inhibit nitric oxide (NO) and cytokine release and inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) expression. The inhibition of these pro-inflammatory factors was associated to Nuclear factor-kB (NF-kB) inhibition. Our results also indicate an anti-oxidant potential of the extract as evidenced by the inhibition of reactive oxygen species (ROS) release and by the activation of the nuclear factor E2-related factor-2 (Nrf-2) pathway in macrophages. The obtained results highlight the anti-inflammatory and antioxidant potential of Lempso extract and its potential use, as a new ingredient for the formulation of functional beverages with high nutraceutical value, providing health benefits to consumers.

Peptidome profiles and bioactivity elucidation of buffalo-milk dairy products after gastrointestinal digestion.

Buffalo milk is highly appreciated for its nutritive properties and highly employed in dairy products, despite this the release of bioactive peptides has not been investigated thoroughly. The aim of this work was to characterize in detail the bioaccesible peptides from buffalo-milk dairy products. Six products were subjected to in vitro simulated gastrointestinal digestion and then analyzed by LC-HRMS. The identified peptides were 165 in Yoghurt, 152 in Scamorza, 146 in Mozzarella, 136 in Grana and Ricotta, 120 in Ice Cream samples, belonging to both buffalo caseins (αs1-, ß-, k-CN) and whey proteins (α-LA, ß-LG). The identified peptide sequences were subjected to a database driven bioactivity search. Results highlighted a wide range of potential bioactive peptides, including antihypertensive, immunomodulatory, antimicrobial, antidiabetic, anticancer and antioxidant activity. These data evidence the content of healthy peptides released from buffalo-milk dairy products and suggest that the specific technological process influence their bioaccessibility.

Chemical profiling of bioactive constituents in hop cones and pellets extracts by online comprehensive two-dimensional liquid chromatography with tandem mass spectrometry and direct infusion Fourier transform ion cyclotron resonance mass spectrometry.

Humulus lupulus L. (hop) is highly interesting from a nutraceutical perspective. The hop phytocomplex contains a wide range of bioactive metabolites, and its characterization is challenging. To tackle such a task, for the first time we applied and compared a combined approach consisting of online comprehensive two-dimensional liquid chromatography with tandem mass spectrometry and direct infusion Fourier transform ion cyclotron mass spectrometry. A reversed phase × reversed phase approach with a shifted gradient in the second dimension ensured selectivity and two-dimensional space coverage. Hyphenation with an ion trap time-of-flight analyzer led to the identification of 83 compounds in 70 min, comprising a novel quercetin derivative and six unknown bitter acids. On the other hand, the direct infusion method was able to identify 40 analytes (except isomers) with high mass accuracy (≤ 0.1 ppm) in less than 1 min analysis time. The developed approach can be used in a complementary way, combining the separation capability and high informative spectra of two-dimensional liquid chromatography tandem mass spectrometry with the ultra-high mass accuracy of direct infusion, for potential compound discovery or the accurate profiling of bioactive compounds in different hop cultivars as well as for monitoring processing and storage of hop-based products.

Flavonoid Composition of Tarocco (Citrus sinensis L. Osbeck) Clone "Lempso" and Fast Antioxidant Activity Screening by DPPH-UHPLC-PDA-IT-TOF.

INTRODUCTION: Clonal selection and hybridisation are valid strategies to obtain fruits with enhanced sensorial and nutraceutical properties. Within Citrus sinensis varieties, Tarocco clone "Lempso" is a typical product of the Calabria region (Italy) characterised by its red pulp. This is the first report concerning its accurate profiling. OBJECTIVE: To characterise in detail the flavonoid composition of Lempso clone and to compare its antioxidant potential with other Citrus varieties by a fast screening method. METHODOLOGY: Extracts were subjected to solid phase extraction and the qualitative/quantitative profile was elucidated through ultra-high performance liquid chromatography (UHPLC) coupled to photodiode array (PDA) and ion trap time-of-flight (IT-TOF) mass spectrometry detection, and compared to both Cleopatra mandarin (Citrus reticulata) and blood orange (Citrus sinensis (L.) Osbeck) Sanguinello varieties. The antioxidant activity was assessed by pre-column 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reaction coupled to UHPLC-PDA. RESULTS: Lempso is characterised by flavonoids (17) and anthocyanins (8). Flavanones content (Hesperidin: 57.19 ± 0.49, Vicenin-2: 4.59 ± 0.03, Narirutin: 5.78 ± 0.13 mg/100 mL) was considerably higher than Cleopatra and Sanguinello varieties. The developed DPPH-UHPLC-PDA method provides information regarding the single contributions to antioxidant activity, highlighting how Ferulic acid, Quercetin and Cyanidin derivatives possess considerable radical scavenging activity (> 50%). The total antioxidant activity was also evaluated and compared with positive controls, showing higher scavenging activity than Cleopatra and Sanguinello (IC50 : 333.76 ± 10.81 µg/mL vs. 452.62 ± 10.81 and 568.39 ± 26.98 µg/mL, respectively). CONCLUSION: These data evidence the nutraceutical potential of Lempso variety, which could be an ingredient for functional beverages. Copyright © 2017 John Wiley & Sons, Ltd.

Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological Activity.

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrussinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value.

Identification of novel microsomal prostaglandin E2 synthase-1 (mPGES-1) lead inhibitors from Fragment Virtual Screening.

Identification of new microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors is currently sought for the treatment of cancer and inflammation. Here we show the results of a Fragment Virtual Screening campaign using the X-ray crystal structure of human mPGES-1 (PDB code: 4AL0). Among the fragments selected and biologically tested, 6 (9H-indeno [1,2-b] [1,2,5]oxadiazolo [3,4-e]pyrazin-9-one) showed the most promising mPGES-1 inhibitory activity (∼30% inhibition at 10 µM). A minimal structure-based optimization of 6 led to compounds 15, 20 and 21, with a promising enhancement of the inhibitory activity (IC50 = 4.6 ± 0.2 µM for 15; IC50 = 2.4 ± 1.0 µM for 20; IC50 = 2.4 ± 0.8 µM for 21). The unprecedented chemical core and the possibility of synthesizing novel derivatives reveal a new and attractive field of action for the development of mPGES-1 inhibitors with potential anti-inflammatory and anticancer properties.