Phloroglucinol Derivatives Research Articles

AKTIVITAS ANTIKANKER SENYAWA ASILFLOROGLUSINOL DARI BIJI Melicope incana TERHADAP SEL KANKER PAYUDARA MCF-7

Melicope incana is one of the plant species that belongs to family Rutaceae. Melicope produces phenolic compounds, including alkaloids, acylphloroglucinol, flavonoids, and coumarins. This study aims to isolate the acyl phloroglucinol derivatives found in M. incana seeds. Extraction of acylphloroglucinol derivatives with methanol using the maceration method at room temperature. Separation and purification using a combination of gravity column chromatography, and radial chromatography. Two acylphloroglucinol compounds have been isolated, namely 3'-geranyl-2',4',6'-trihydroxy acetophenone ( 1 ) and 3'-isoprenyl-2',4',6'-trihydroxy acetophenone ( 2 ). The structure of the two compounds was determined based on UV, IR, 1D, and 2D NMR spectroscopic analysis. Anticancer activity of compounds 1-2 against breast cancer cells MCF-7 showed IC 50 values of 48.98 and 4.30 µg /mL, respectively.

Two New Phloroglucinol Derivatives from Syzygium brachyantherum

Two new phloroglucinol derivatives were isolated from the twigs and leaves of Syzygium brachyantherum. Their structures were elucidated based on extensive spectroscopic data. They exhibited weak inhibitory activities against α-glucosidase and PTP1B.

Toward an efficient and eco-friendly route for the synthesis of dimeric 2,4-diacetyl phloroglucinol and its potential as a SARS-CoV-2 main protease antagonist: insight from in silico studies

Dimeric 2,4-diacetyl phloroglucinol derivatives were synthesized under green chemistry protocols and found to be the potential inhibitor of 3CLpro of SARS-CoV-2.

The discovery of new phloroglucinol glycosides from Agrimonia pilosa and the mechanism of oxidative dearomatization of the methyl-substituted phloroglucinol derivatives.

Six methyl-substituted phloroglucinol glycosides (1–6) were isolated from Agrimonia pilosa, including four new compounds (1–3, 6). The aglycones (1a–4a) of 1–4 and their corresponding oxidized products (1c–4c) were also obtained from A. pilosa. The structures were determined by a series of spectroscopic analyses and chiral separation. Notably, the structures of aglycones 1a–4a were unstable and prone to oxidation spontaneously, to yield the dearomatized structures 1c–4c. The mechanism of oxidative dearomatization was disclosed as a free-radical chain reaction with 3O2 by the techniques of HPLC-HR-MS2, EPR spectra and DFT-calculation, and hydroperoxide was defined as the intermediate.

Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors.

Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3′ is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1–4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.

Cytotoxic polyprenylated phloroglucinol derivatives from Hypericum elodeoides Choisy modulating the transactivation of RXRα

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E–F (2–3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1–3 were proposed.

UPLC-PDA-Q Exactive Orbitrap-MS profiling of the lipophilic compounds product isolated from Eucalyptus viminalis plants

The lipophilic compounds product (LCP), which was isolated and purified from Eucalyptus viminalis plants, has shown earlier broad antimicrobial and anti-inflammatory activities. To study secondary compounds responsible for the pharmacological activities, chemical composition of the LCP was studied with application of ultra-performance liquid chromatography combined with photodiode array detector and high-resolution Q Exactive Orbitrap mass spectrometer (UPLC-PDA-HRMS/MS). There were found thirty two compounds: twenty phloroglucinol derivatives (isopentyl diformyl phloroglucinol, macrocarpals, sideroxylonals, etc.), eight ursane type triterpenoids (loxanic acid, dehydroursolic acid lactone, dehydroursolic acid lactone acetate, two isomers of p-coumaroyl-dehydroursolic acid lactone and two isomers of feruloyl-dehydroursolic acid lactone), sequiterpenoid (S)-β-macrocarpene and three unknown phenolics. The major compounds of the LCP were pharmacologically active macrocarpals A and B, dehydroursolic acid lactone and its derivatives. It is supposed that previously discovered antimicrobial and anti-inflammatory activities of the LCP is due to the high contents of these secondary compounds.

Isolation and Purification of Five Phloroglucinol Derivatives From Agrimonia Pilosa Ledeb by Counter-Current Chromatography Using Non-Aqueous Solvent Systems

Five non-polar phloroglucinol derivatives, viz. pseudo-aspidin, α-kosin and agripinol A-C were isolated and purified from Agrimonia pilosa Ledeb by semi-preparative counter-current chromatography. The separation was performed by a two-step elution with non-aqueous solvent systems. In the first step, an elution mode of a two-phase solvent system consisting of n-hexane-acetonitrile-dichloromethane-methanol (6:6:0.5:0.5, v/v/v/v) was used. We obtained sample Ι containing three components (47.0mg) and sample ΙΙ containing two components (24.8mg) from crude extract (371.0mg). In the second step, sample Ι was successfully separated by closed-loop recycling mode with a solvent system consisting of n-hexane-acetonitrile-dichloromethane (10:7:3, v/v/v), yielding 17.8mg of pseudo-aspidin, 18.5mg of α-kosin and 6.4mg of agripinol A. The other two compounds-8.7mg of agripinol B and 13.6mg of agripinol C-were obtained from sample ΙΙ in the same manner. All the isolated compounds had a high purity exceeding 95%.

Effect of Fruit Secondary Metabolites on Melanoma: A Systematic Review of In vitro Studies

Background: Melanoma is a highly aggressive form of skin cancer and is responsible for the majority of the deaths related to this pathology. Recently, different studies have identified naturally occurring compounds of fruits with chemopreventive action. This systematic review aims to investigate the protective role of fruit phytochemicals against melanoma skin cancer from in vitro studies. Methods: The articles were selected using the search terms string "skin neoplasms" OR “melanoma” AND “fruit” in the following databases: Pubmed/Medline, Bireme, Web of Science and ScienceDirect. Results: Out of an initial database search of 391 titles and/or abstracts, 115 full-text articles were eligible and after final evaluation 49 were selected for further assessment. Almost all analysed articles reveal that compounds of different classes (alkaloid, alkane, benzopyrone, cyclopenta[b]benzofuran, ester, flavonoid, tocotrienols, phenolic, phenylpropanoid, phloroglucinol derivative, terpenoids and betalain) possess anti-melanoma in vitro activity. The benzopyrone (α-mangostin) and stilbene (resveratrol) were effective in inhibiting melanoma cell metastasis, essential to stop the progression of malignant cells. Conclusion: Phytochemicals that possess anticancer properties are present in both, common and exotic fruits. Some of these novel compounds are considered as promising starting points for the discovery of effective new drugs.

Humulone Modulation of GABAA Receptors and Its Role in Hops Sleep-Promoting Activity.

Humulus lupulus L. (hops) is a major constituent of beer. It exhibits neuroactive properties that make it useful as a sleeping aid. These effects are hypothesized to be mediated by an increase in GABAA receptor function. In the quest to uncover the constituents responsible for the sedative and hypnotic properties of hops, recent evidence revealed that humulone, a prenylated phloroglucinol derivative comprising 35–70% of hops alpha acids, may act as a positive modulator of GABAA receptors at low micromolar concentrations. This raises the question whether humulone plays a key role in hops pharmacological activity and potentially interacts with other modulators such as ethanol, bringing further enhancement in GABAA receptor-mediated effects of beer. Here we assessed electrophysiologically the positive modulatory activity of humulone on recombinant GABAA receptors expressed in HEK293 cells. We then examined humulone interactions with other active hops compounds and ethanol on GABA-induced displacement of [3H]EBOB binding to native GABAA receptors in rat brain membranes. Using BALB/c mice, we assessed humulone’s hypnotic behavior with pentobarbital- and ethanol-induced sleep as well as sedation in spontaneous locomotion with open field test. We demonstrated for the first time that humulone potentiates GABA-induced currents in α1β3γ2 receptors. In radioligand binding to native GABAA receptors, the inclusion of ethanol enhanced humulone modulation of GABA-induced displacement of [3H]EBOB binding in rat forebrain and cerebellum as it produced a leftward shift in [3H]EBOB displacement curves. Moreover, the additive modulatory effects between humulone, isoxanthohumol and 6-prenylnaringenin were evident and corresponded to the sum of [3H]EBOB displacement by each compound individually. In behavioral tests, humulone shortened sleep onset and increased the duration of sleep induced by pentobarbital and decreased the spontaneous locomotion in open field at 20 mg/kg (i.p.). Despite the absence of humulone effects on ethanol-induced sleep onset, sleep duration was increased dose-dependently down to 10 mg/kg (i.p.). Our findings confirmed humulone’s positive allosteric modulation of GABAA receptor function and displayed its sedative and hypnotic behavior. Humulone modulation can be potentially enhanced by ethanol and hops modulators suggesting a probable enhancement in the intoxicating effects of ethanol in hops-enriched beer.

Hypericum scruglii Bacch., Brullo & Salmeri, a Potential Natural Remedy for Fibromyalgia: A Narrative Review

Fibromyalgia (FM) is a disorder of central pain processing marked by widespread chronic pain together with fatigue, sleep disturbances, cognitive dysfunction, and depressive episodes. Tested treatments have expressed limited efficacy. Oxidative stress plays a role in the pathology of FM, while multiple neurotransmitters are involved in this syndrome. Antidepressants are used as conventional treatment, especially those with double action on serotonin and norepinephrine that leads to an increased risk of a manic switch. It should be noted that fibromyalgia is high-frequency comorbidity in bipolar disorder. This narrative review, given the limited literature, consisted of animal and in vitro studies, which aims to highlight the positive aspects of Hypericum scruglii as a potential remedy against FM. Many in vitro and clinical studies confirm the Hypericum genus as a natural antidepressant resource. The use of Hypericum derivatives in various acute and chronic diseases has been known for a long time. It is reported that the phloroglucinol derivatives from Hypericum longistylum improve and accelerate the differentiation of neural progenitor cells. The advantage of Hypericum scruglii is that it owns greater antioxidant potential than other species of the Hypericum genus. Suggestions for improving the oral bioavailability of very poor water-soluble molecules of hypericum extracts are also described in this paper.

Five new phloroglucinol derivatives from Syzygium brachyantherum and their α-glucosidase and PTP1B inhibitory activities

Five new phloroglucinol derivatives were isolated from Syzygium brachyantherum, and their structures were elucidated as brachyanones A–E (1–5) on the basis of the extensive spectroscopic analysis. Among them, compounds 1 and 3 exhibited significant inhibitory activity against α-glucosidase with IC50 of 2.57 and 0.97 μM, respectively. Furthermore, compound 4 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory effect with inhibition ratio of 89.42% at 100 μM. This discovery indicates that phloroglucinol derivatives with long aliphatic chain possibly play an important role in antidiabetic activity of Syzygium plants, and they could function as a promising antidiabetic agent.

Potent and Non-Cytotoxic Antibacterial Compounds Against Methicillin-Resistant Staphylococcus aureus Isolated from Psiloxylon mauritianum, A Medicinal Plant from Reunion Island.

With the occurrence of antibiotic-resistant Staphylococcus aureus strains, identification of new anti-staphylococcal drugs has become a necessity. It has long been demonstrated that plants are a large and diverse source of antibacterial compounds. Psiloxylon mauritianum, an endemic medicinal plant from Reunion Island, was chemically investigated for its reported biological activity against S. aureus. Aspidin VB, a phloroglucinol derivative never before described, together with Aspidin BB, were first isolated from the ethyl acetate extract of P. mauritianum leaves. Their structures were elucidated from spectroscopic data. Aspidin VB exhibited strong antibacterial activity against standard and methicillin-resistant S. aureus strains, with a minimal inhibition concentration (MIC) of 0.25 μg/mL, and no cytotoxicity was observed at 10−5 M in MRC5 cells. Due to its biological activities, Aspidin VB appears to be a good natural lead in the fight against S. aureus.

Phloroglucinol Derivatives from Myrtus communis 'Variegata' and Their Antibacterial Activities.

Myrtucomvalones D-F, three new triketone-phloroglucinol-triketone adducts, and three known ones (myrtucommulone E, myrtucommulone D and callistenone D) were obtained from Myrtus communis 'Variegata'. Myrtucomvalone D is a pair of enantiomers which was further resolved into (+)-myrtucomvalone D and (-)-myrtucomvalone D by chiral HPLC. Their structures and complete stereochemistry were established from interpretation of NMR and crystallographic data and chemical calculations. Myrtucomvalone F, myrtucommulone D and callistenone D showed significant antibacterial activities.

Sc(OTf)3-Catalyzed Synthesis of Symmetrical Dithioacetals and Bisarylmethanes Using Nitromethane as a Methylene Source.

Use of nitromethane as an electrophilic methylene source for the synthesis of symmetrical dithioacetals and bisarylmethanes has been showcased using Sc(OTf)3 as a catalyst. The procedure allows straightforward access to the densely functionalized dithioacetals and bisarylmethanes under mild conditions. Additionally, the method has been applied for the synthesis of antimalarial tetramethyl mellotojaponin C and anticancer dimeric phloroglucinol derivative.

Phenolic Constituents of Syzygium austroyunnanense

Twelve phenolic compounds, including one new phloroglucinol derivative, were isolated from the leaves of Syzygium austroyunnanense. Their structures were elucidated based on the spectroscopic data and by comparison with the literature. All of compounds were firstly isolated from this species.

Hypericum scruglii Bacchetta, Brullo & Salmeri, is it a possible natural resource against Fibromyalgia?

Fibromyalgia (FM) is today a serious public health issue. Tested treatments have shown limited efficacy. Oxidative stress probably interacting with the glutamatergic / gamma - Aminobutyric acid balance may play a role. Antidepressants improve sleep and mood especially those with double action on serotonin and norepinephrine, but these are also those with a greater risk of manic switch considering the high frequency of comorbidity with bipolar disorders. This narrative review tries to evaluate, on the basis of in vitro and animal studies, the potential utility in fibromyalgia of Hypericum Scruglii, an endemic species peculiar to the island of Sardinia. The studies that have verified the antidepressant efficacy of Hypericum Perforatum and the first attempts of its use in fibromyalgia are reported as well as the studies that found the phloroglucinol derivatives from Hypericum longistylum (well-known in traditional Chinese medicine) that facilitate the differentiation of neural progenitor cells, and increase the efficiency of differentiation into serotonergic neurons. The advantage of Hypericum Scruglii may be represented by the anti-oxidant potential revealed to be greater than in other species of the same genus. The paper also describes new approaches to improving the oral bioavailability of very poor water-soluble molecules of hypericum extracts.

Phloroglucinols from Myrtaceae: attractive targets for structural characterization, biological properties and synthetic procedures

Myrtaceae Juss. is a very large family of flowering plants, that are a valuable source of bioactive compounds. From the phytochemical point of view, apart from ubiquitous tannins, flavonoid derivatives and volatile oils, Myrtaceae plants are very rich in phloroglucinol derivatives, divided in two principal subclasses: oligomeric acylphloroglucinols and phloroglucinol-terpene adducts. Despite this large structural variability, many studies on phloroglucinols from the Myrtaceae have focused on unique bioactive acylphloroglucinol compounds, named myrtucommulones. Nevertheless, many studies also reported other interesting phloroglucinol derivatives. Therefore, in this review, a comprehensive description of the chemical features of acylphloroglucinols and meroterpenoid-acylphloroglucinols from the Myrtaceae family is presented along with their biological activities. Moreover, since myrtucommulones and their derivatives have become attractive targets for organic chemists, thanks to their structural features and biological activities, relevant approaches and synthetic procedures are herewith discussed.

Eckol from Ecklonia cava Suppresses Immunoglobulin E-mediated Mast Cell Activation and Passive Cutaneous Anaphylaxis in Mice.

Eckol, a precursor compound belonging to the dibenzo-1,4-dioxin class of phlorotannins, is a phloroglucinol derivative that exerts various activities. In the present study, we investigated the antiallergic effects of eckol isolated from the marine brown algae, Ecklonia cava using immunoglobulin E (IgE)/bovine serum albumin (BSA)-stimulated mouse bone marrow-derived cultured mast cells (BMCMC) and a mouse model of anaphylaxis. Eckol inhibited IgE/BSA-induced BMCMC degranulation by reducing β-hexosaminidase release. A flow cytometric analysis revealed that eckol decreases FcεRI expression on cell surface and IgE binding to the FcεRI in BMCMC. Moreover, eckol suppressed the production of the cytokines, interleukin (IL)-4, IL-5, IL-6, and IL-13 and the chemokine, thymus activation-regulated chemokine (TARC) by downregulating, IκB-α degradation and NF-κB nuclear translocation. Furthermore, it attenuated the passive cutaneous anaphylactic reaction induced by IgE/BSA-stimulation in the ear of BALB/c mice. These results suggest that eckol is a potential therapeutic candidate for the prevention and treatment of allergic disorders.

Novel phloroglucinol derivative Compound 21 protects experimental autoimmune encephalomyelitis rats via inhibiting Th1/Th17 cell infiltration

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among the factors involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel phloroglucinol derivative, significantly protected myelin from damage in our previous study. However, it remains unclear whether this compound affects MS. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuates neurological deficits, immune infiltration, and demyelination in EAE rats. Our mechanistic investigation revealed that Compound 21 treatment reduces the population of Th1/Th17 cells and inhibits their infiltration into the CNS. Furthermore, we found that the inhibition of Th1/Th17 cell infiltration is related to the direct suppression of Th1/Th17 cell differentiation and the inhibition of proinflammatory microglial cells. Collectively, these results confirm that Compound 21 suppresses infiltrated Th1/Th17 cells to alleviate demyelination in EAE rats, suggesting its potential role as a novel candidate for MS treatment.