Methyl Orsellinate Research Articles

A New Brominated Isocoumarin from the Marine Starfish-Associated Fungus Aspergillus sp. WXF1904.

Based on the one strain many compounds strategy, a new brominated isocoumarin, 5-bromo-6,8-dihydroxy-3,7-dimethylisocoumarin (1), along with four new natural products, methyl 3-bromo-2,4-dihydroxy-6-methylbenzoate (2), methyl 2-bromo-4,6-dihydroxybenzoate (3), (E)-3-(3-bromo-4-hydroxyphenyl) acrylic acid (4) and 4-hydroxy-3-methyl-6-phenyl-2H-pyran-2-one (5), and four known compounds, methyl orsellinate (6), 4-hydroxy-3-methyl-6-(1-methyl-1-propenyl)-2H-pyran-2-one (7), pilobolusate (8) and cis-ferulic acid (9), were isolated from the ethyl acetate extract of the fungus Aspergillus sp. WXF1904 under the condition of adding bromine salt to the production medium. The structures of the new compounds were established by analysis of NMR and MS data. Compounds (1-9) were evaluated for inhibitory activity of acetylcholinesterase and pancreatic lipase, the new compound 1, known compounds 6 and 7 displayed weak inhibitory activity against acetylcholinesterase, compounds 2, 5, 7 and 8 showed weak inhibitory activity against pancreatic lipase.

A New 3-Benzylphthalide from the Moss Erythrodontium julaceum.

From the moss Erythrodontium julaceum Paris growing in Vietnam, julacelide (1), a new 3-benzylphthalide, along with methyl orsellinate (2), ethyl orsellinate (3), 4-O-methylhaematommic acid (4), and zeorin (5), were isolated and structurally elucidated. Their chemical structures were elucidated through extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as through comparisons to the existing literature. Compound 4-O-methylhaematommic acid was a new natural product. The absolute configuration of julacelide was defined using time-dependent density functional theory (TDDFT) calculations. Julacelide was evaluated for α-glucosidase inhibition.

Screening for Novel Type 2 Ryanodine Receptor Inhibitors by Endoplasmic Reticulum Ca2+ Monitoring.

Type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic (ER)/sarcoplasmic reticulum that plays a central role in the excitation-contraction coupling in the heart. Hyperactivity of RyR2 has been linked to ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia and heart failure, where spontaneous Ca2+ release via hyperactivated RyR2 depolarizes diastolic membrane potential to induce triggered activity. In such cases, drugs that suppress RyR2 activity are expected to prevent the arrhythmias, but there is no clinically available RyR2 inhibitors at present. In this study, we searched for RyR2 inhibitors from a well-characterized compound library using a recently developed ER Ca2+-based assay, where the inhibition of RyR2 activity was detected by the increase in ER Ca2+ signals from R-CEPIA1er, a genetically encoded ER Ca2+ indicator, in RyR2-expressing HEK293 cells. By screening 1535 compounds in the library, we identified three compounds (chloroxylenol, methyl orsellinate, and riluzole) that greatly increased the ER Ca2+ signal. All of the three compounds suppressed spontaneous Ca2+ oscillations in RyR2-expressing HEK293 cells and correspondingly reduced the Ca2+-dependent [3H]ryanodine binding activity. In cardiomyocytes from RyR2-mutant mice, the three compounds effectively suppressed abnormal Ca2+ waves without substantial effects on the action-potential-induced Ca2+ transients. These results confirm that ER Ca2+-based screening is useful for identifying modulators of ER Ca2+ release channels and suggest that RyR2 inhibitors have potential to be developed as a new category of antiarrhythmic drugs. SIGNIFICANCE STATEMENT: We successfully identified three compounds having RyR2 inhibitory action from a well-characterized compound library using an endoplasmic reticulum Ca2+-based assay, and demonstrated that these compounds suppressed arrhythmogenic Ca2+ wave generation without substantially affecting physiological action-potential induced Ca2+ transients in cardiomyocytes. This study will facilitate the development of RyR2-specific inhibitors as a potential new class of drugs for life-threatening arrhythmias induced by hyperactivation of RyR2.

Molecular docking and dynamics supported investigation of antiviral activity of Lichen metabolites of Roccella montagnei: an in silico and in vitro study

Lichens are symbiotic organisms that have been traditionally used for treating different kinds of ailments. As there are only a few reports on the antiviral activity of lichens, we thought of evaluating the anti-Herpes simplex virus-1 (HSV-1) activity of methanolic extract of Roccella montagnei and their isolated compounds. Fractionation of crude methanolic extract of Roccella montagnei by column chromatography isolated two pure compounds. Antiviral activity was assessed using a CPE inhibition assay at non-cytotoxic concentrations on Vero cells. Molecular docking and dynamics studies were carried out against Herpes simplex type-1 thymidine kinase to understand the binding interactions of the isolated compounds with reference to acyclovir. Isolated compounds were characterized as methyl orsellinate and montagnetol by spectral methods. Methanolic extract of Roccella montagnei exhibited an EC50 value of 56.51 µg/ml, while the compounds methyl orsellinate and montagnetol offered EC50 values of 13.50 µg/ml and 37.52 µg/ml, respectively, against HSV-1 viral infection on Vero cell lines. The selectively index (SI) of montagnetol (10.93) was found to be higher when compared to that of methyl orsellinate (5.55), indicating its better anti-HSV-1 activity. The docking and dynamics studies showed montagnetol was stable throughout the 100 ns, having better interactions and docking scores with HSV-1 thymidine kinase than methyl orsellinate, as well as the standard. To understand the mechanism of montagnetol’s anti-HSV-1 activity, more research is required, and this could lead to the discovery of new and effective antiviral agents. Communicated by Ramaswamy H. Sarma

In Silico Pharmacokinetic Profiling of the Identified Bioactive Metabolites of Pergularia tomentosa L. Latex Extract and In Vitro Cytotoxic Activity via the Induction of Caspase-Dependent Apoptosis with S-Phase Arrest.

The in vitro cytotoxic efficacy of plant latex from Pergularia tomentosa L. was studied using five human cancer cell lines: HeLa cells (cervical carcinoma cells), A-549 (lung carcinoma), Panc-1 (pancreatic carcinoma cells), MDA-MB-231 (metastatic mammary adenocarcinoma), and MRC-5 (lung fibroblast cell line) cells. The phytonutrient content of plant latex was identified using the liquid chromatography/mass spectra-quadrupole time of flight (LC/MS-QTOF) technique. In silico studies of polyphenols were carried out to clarify the potential mode of action of the plant latex’s constituents. The treatment of different tumor cell lines with different concentrations of plant latex revealed a potent efficacy on the human lung carcinoma cell line (A-549) (IC50 = 3.89 µg/mL) compared with that with vinblastine as a positive control (IC50 = 7.12 µg/mL). The effect of the potent concentration of plant latex on the A-549 cell line induced cell arrest, upregulated the expression of pre-apoptotic markers, and downregulated the expression of antiapoptotic markers. Seven identified polyphenols were selected for the in silico study. A docking assessment using the epidermal growth factor receptor kinase (EGFRk) and eltronib as a positive control showed a higher affinity for the enzyme receptor of the selected polyphenols, except for methyl orsellinate and ginkgotoxin. The ADMET assessment demonstrated the inhibitory effect of the polyphenols on CYP450, except for ouabagenin and xanthyletine. The selected polyphenols obey Lipinski’s drug-likeness with no significant toxicity effect. In conclusion, the plant latex of P. tomentosa L. showed cytotoxic activity on the A-549 cell line, and the selected polyphenols showed a promising prodrug agent with a low profile of toxicity in the study.

Antibiotic and Nematocidal Metabolites from Two Lichen Species Collected on the Island of Lampedusa (Sicily).

The antibiotic and nematocidal activities of extracts from two coastal lichen species collected on Lampedusa Island (Sicily), Ramalina implexa Nyl. and Roccella phycopsis Ach., were tested. Methyl orsellinate, orcinol, (+)-montagnetol, and for the first time 4-chlororcinol were isolated from Roccella phycopsis. (+)-Usnic acid was obtained from Ramalina implexa. The crude organic extract of both lichen species showed strong antibiotic activity against some bacterial species and nematocidal activity. Among all the pure metabolites tested against the infective juveniles (J2) of the root-knot nematode (RKN) Meloydogine incognita, (+)-usnic acid, orcinol, and (+)-montagnetol had significant nematocidal activity, comparable with that of the commercial nematocide Velum® Prime, and thus they showed potential application in agriculture as a biopesticide. On the contrary, methyl orsellinate and 4-chlororcinol had no nematocidal effect. These results suggest that the substituent pattern at ortho-para-position in respect to both hydroxyl groups of resorcine moiety, which is present in all metabolites, seems very important for nematocidal activity. The organic extracts of both lichens were also tested against some Gram-positive and Gram-negative bacteria. Both extracts were active against Gram-positive species. The extract of Ramalina implexa showed, among Gram-negative species, activity against Escherichia coli and Acinetobacter baumannii, while that from Roccella phycopsis was effective towards all test strains, with the exception of Pseudomonas aeruginosa. The antimicrobial activity of (+)-usnic acid, methyl orsellinate, and (+)-montagnetol is already known, so tests were focused on orcinol and 4-chlororcinol. The former showed antibacterial activity against all Gram positive and Gram-negative test strains, with the exception of A. baumannii and K. pneumoniae, while the latter exhibited a potent antibacterial activity against Gram-positive test strains and among Gram-negative strains, was effective against A. baumannii and K. pneumonia. These results suggest, for orcinol and 4-chlororcinol, an interesting antibiotic potential against both Gram-positive and Gram-negative bacterial strains.

Anti-Inflammatory Potential of Compounds Isolated from Tunisian Lichens Species.

The lichen's special symbiotic structure enables it to produce bioactive substances. They have historically been recognized for their aesthetic and medicinal benefits. Furthermore, in recent years, they have performed in various fields, including perfumery, dyeing, and pharmacology due to their rich secondary metabolites. From our study, four compounds were isolated from organic extracts of Parmotrema hypoleucinum, Roccella phycopsis, and Xanthoria parietina and identified by spectroscopic investigation as atranorin, (+)-iso-usnic acid, methyl orsellinate, and parietin, respectively. The anti-inflammatory effects of lichens extracts, and pure compounds were evaluated on RAW 264.7 macrophages cells at different concentrations. At 25 μg/mL all treated samples did not show any effect on cell viability. Atranorin and (+)-iso-usnic acid showed an inhibitory effect on nitric oxide (NO) levels in lipopolysaccharide (LPS)-stimulated macrophages. Nitric oxide (NO) production was measured using Griess reagent, atranorin and (+)-iso-usnic acid showed a high anti-inflammatory potential (75.99 % and 57.27 % at 25 μg/mL). On the other hand, methyl orsellinate and the organic extracts of three lichens showed good anti-inflammatory activity ranging from 29.16 % at 25 μg/mL to 86.91 % at 100 μg/mL.

Biological Activities of Lichen-Derived Monoaromatic Compounds.

Lichen-derived monoaromatic compounds are bioactive compounds, associated with various pharmacological properties: antioxidant, antifungal, antiviral, cytotoxicity, and enzyme inhibition. However, little is known about data regarding alpha-glucosidase inhibition and antimicrobial activity. Very few compounds were reported to have these activities. In this paper, a series of monoaromatic compounds from a lichen source were isolated and structurally elucidated. They are 3,5-dihydroxybenzoic acid (1), 3,5-dihydroxybenzoate methyl (2), 3,5-dihydroxy-4-methylbenzoic acid (3), 3,5-dihydroxy-4-methoxylbenzoic acid (4), 3-hydroxyorcinol (5), atranol (6), and methyl hematommate (7). To obtain more derivatives, available compounds from the previous reports such as methyl β-orsellinate (8), methyl orsellinate (9), and D-montagnetol (10) were selected for bromination. Electrophilic bromination was applied to 8–10 using NaBr/H2O2 reagents to yield products methyl 5-bromo-β-orsellinate (8a), methyl 3,5-dibromo-orsellinate (9a), 3-bromo-D-montagnetol (10a), and 3,5-dibromo-D-montagnetol (10b). Compounds were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 4 showed stronger alpha-glucosidase inhibition than others with an IC50 value of 24.0 µg/mL. Synthetic compound 9a exhibited remarkable activity against Staphylococcus aureus with a MIC value of 4 µg/mL. Molecular docking studies were performed to confirm the consistency between in vitro and in silico studies.

Usneaceratins A and B, two new secondary metabolites from the lichen Usnea ceratina

Two new compounds, comprising one dibenzofuran, named usneaceratin A (1), and one phenolic acid, named usneaceratin B (2), together with one known dibenzofuran, isousnic acid (3), and two known phenolics, orsellinic acid (4) and methyl orsellinate (5) were clarified from the lichen Usnea ceratina using variously chromatographic methods. Their structures were testified by comprehensive HR-ESI-MS, and NMR spectroscopic analysis, and comparison with published data. Their α-glucosidase inhibitory activity of all compounds was measured. Usneaceratin B (2) possessed better inhibition against α-glucosidase enzyme (IC50 value of 41.8 μM) than the standard drug acarbose (IC50 value of 214.50 μM).

Phenolic compounds from the lichen Parmotrema tinctorum

Introduction: The metabolites of lichens concentrated depsidones, depsides, and diphenyl ethers were possessed antibiotic, antifungal, antiviral, antitumor, and anticancer activities. Parmotrema tinctorum (Despr. ex Nyl.) Hale, a species of foliose lichen, is widely distributed in Lam Dong province, Vietnam. Herein, this paper describes the isolation and structure elucidation of seven compounds isolated from this lichen. Methods: Phytochemical investigations of the ethyl acetate extract of the lichen P. tinctorum led to the isolation of seven pure compounds. Their chemical structures were elucidated by extensive HR-ESI-MS and NMR spectroscopic analysis and comparison with previously published data. Results: Seven compounds, namely orcinol (1), orsellinic acid (2), methyl orsellinate (3), methyl heamatomate (4), lecanorin (5), lecanoric acid (6), and gyrophoric acid (7). These compounds were determined the α-glucosidase inhibitory activity. Conclusions: Compound 7 was determined for the first time in P. tinctorum, and this was also the first time these compounds were determined the α-glucosidase inhibitory activity.

Investigation of chemical constituents and cytotoxic activity of the lichen Usnea undulata

AbstractLichens are a promising source of good anticancer agents. However the study on their bioactivities remains limited, especially in Vietnam. In this study, three extracts of lichen Usnea undulata Stirt. including n‐hexane, acetone and methanol were investigated for their cytotoxic activity on two human cancer cell lines (MCF‐7, NCI‐H460) and normal fibroblasts by sulforhodamine B (SRB) assay. The results showed that the n‐hexane extract exhibited the highest inhibition activity with IC50 5.26±0.13 μg/mL for MCF‐7 and 6.83±0.64 μg/mL for NCI‐H460, followed by acetone extract with IC50 66.44±1.37 μg/mL and 92.14±1.49 μg/mL, respectively. The methanol extract possessed weak cytotoxic effect against MCF‐7 and NCI‐H460 (IC50 values more than 100 μg/mL). The n‐hexane extract demonstrated interesting activity particularly on MCF‐7 as good selectivity index was recorded (SI > 3). The phytochemical study on n‐hexane and acetone extracts led to the isolation of four compounds including usnic acid (1), methyl orsellinate (2), methyl β‐orsellinate (3), 7‐hydroxyl‐5‐methoxy‐6‐methylphtalide (4) in which compound (4) was isolated the first time in such species. Their structures were elucidated by NMR analysis and compared with literature data.

Identification of Anti-Helicobacter pylori Compounds From Usnea undulata:

In this study, we evaluated 3 extracts (n-hexane, acetone, and methanol) of Usnea undulata Stirton (Usneaaceae) and 5 isolated compounds [methyl orsellinate (1), methyl β-orsellinate (2), 7-hydroxy...

Identification of Anti-Helicobacter pylori Compounds From Usnea undulata

In this study, we evaluated 3 extracts ( n-hexane, acetone, and methanol) of Usnea undulata Stirton (Usneaaceae) and 5 isolated compounds [methyl orsellinate (1), methyl β-orsellinate (2), 7-hydroxyl-5-methoxy-6-methylphtalide (3), usnic acid (UA) (4), and salazinic acid (5)] for their inhibitory activity against Helicobacter pylori. The results showed that the n-hexane extract exhibited the strongest activity with the largest inhibition zone ( d = 14 mm). For the isolated metabolites, besides UA that has been reported as a potent anti- H. pylori agent, compounds 1 and 2 showed higher inhibition compared to the reference drugs. Our results demonstrated that U. undulata could be a promising source of potential anti- H. pylori metabolites.

A new epicatechin glucopyranoside derivative from Styrax suberifolius

A new derivative of epicatechin glucopyranoside, (2R,3R)-3,7,4'-trihydroxy-5,3'-dimethoxyflavan 7-O-β-d-glucopyranoside (1), together with three mononuclear phenolic acid esters, methyl orsellinate (2), ethyl orsellinate (3) and methyl β-orcinolcarboxylate (4) were isolated from the bark of Styrax suberifolius. The structures of 1–4 were determined on the basis of extensive analysis of NMR and MS spectra combined with chemical hydrolysis. The antifungal activities of the isolated compounds against three plant pathogenic fungi, Alternaria solani, Fusarium oxysporum and Phomopsis cytospore were evaluated using radial growth inhibition assay. Compounds 2, 3 and 4 exerted selective inhibitory activities against the tested fungi. Among of them, methyl β-orcinolcarboxylate (4) exhibited obvious inhibitory effect against P. cytospore, with an inhibition rate of 86.72% at 100 μg/ml.

Chemical constituents of the stem barks of Swintonia floribunda Griff. (Anacardiaceae)

Swintonia floribunda Griff. is an evergreen tree that belongs to Anacardiaceae family, which grows at Tay Nguyen, Lam Dong, and Dong Nai Provinces in Vietnam. Swintonia floribunda showed many interesting biological activities such as antitumor effect against breast and pancreatic cancers, antioxidant, and antimicrobial activities. From the stem barks of Swintonia floribunda Griff. (Anacardiaceae) collected in Dong Nai province, three epoxylignans: pinoresinol (1), syringaresinol (2), epipinoresinol (3), together with three other compounds: n-heptacosyl trans-ferulate (4), methyl orsellinate (5), and friedelin (6) have been isolated from the EtOAc-soluble extract. The chemical structure of these compounds were determined by 1D and 2D NMR spectra and comparison with published data. These compounds were first reported in Swintonia floribunda

Secondary metabolites from lichen Usnea longissima and its pharmacological relevance

The objective of the study was to isolate chemical compounds from lichen Usnea longissima (UL) and to use lichen metabolites as antibiotics, antifungal, anti-HIV, anticancer, antiprotozoan, and antibacterial agents. Preparation of the lichen extracts: Fine powder of UL lichen was extracted using acetone, methanol, and water in a Soxhlet extractor. In a rotary evaporator, the extracts were filtered and then concentrated under reduced pressure. The dry extracts were stored at 18°C until they were used in the tests. The extracts were used for various assays. Sixteen compounds were isolated from lichen UL using various chromatographic techniques, including silica gel, Sephadex LH-20, operational data store, and semipreparative high-performance liquid chromatography. By spectroscopic data analyses, their structures were identified as (1) useanol, (2) lecanorin, (3) 3-hydroxy-5-methylphenyl 2-hydroxy-4-methoxy-6-methylbenzoate, (4) lecanorin E, (5) 3'-methylevernic acid, (6) evernic acid, (7) barbatinic acid, (8) 3,7-dihydroxy-1,9-dimethyldibenzofuran, (9) orcinol, (10) O-methyl orcinol, (11) methyl orsellinate, (12) methyl everninate, (13) 2,5-dimethyl-1,3-benzenediol, (14) 2-hydroxy-4-methoxy-3,6-dimethyl benzoic acid, (15) ethyl everninate, and (16) ethyl 2,4-dihydroxy-6-methylbenzoate. UL lichen is a great source of secondary metabolites, which can be used as antimicrobial, antiproliferative, and anticancer agents. This lichen can be used as a natural antioxidant or antitumor agent in clinical practice; commercially, it can be used as an anticancer drug.

Chemical profile and biological activities of Peltigera horizontalis (Hudson) Baumg. thallus and apothecia extracts

The aim of this study was to determine, for the first time, the chemical composition of Peltigera horizontalis thallus and apothecia extracts (ether, ethyl acetate, dichloromethane and acetone) by HPLC-UV and GC-MS, and evaluate activity of genotoxic, anticholinesterase, antioxidant and antibacterial potential of acetone extracts. Major constituents of thallus extracts were gyrophoric acid, and methyl gyrophorate while dominant component of apothecia extracts was tenuiorin. The predominant volatile compounds in extracts were methyl orsellinate, dodecyl acrylate, orcinol and orcinol monomethyl ether. The thallus acetone extract at concentration of 2.0 µg mL−1 gave the greatest decrease in the micronuclei frequency (22.4%) of all tested extracts. Apothecia extract showed stronger antioxidant activity as compared to thallus extract. Tested extracts at concentration of 10 mg mL−1 exhibited inhibitory effect (16.5% for thallus and 12.8% for apothecia) on pooled human serum cholinesterase. P. horizontalis acetone extracts had no activity against the tested five bacteria strains.

Three new polyketides from fruiting bodies of the endophytic ascomycete Xylaria polymorpha

The isolation of three new secondary metabolites from the fruiting body of Xylaria polymorpha is described. The new compounds are of mixed biosynthetic origin consisting of a polyketide starter, extended with a methyl orsellinate unit and terminated hydrolytically or with an amine-containing terminal unit.

Diphenyl ethers and indanones from the soil-derived fungus Aspergillus unguis PSU-RSPG204

Two new indanones, asperunguisones A-B (1–2), and three new diphenyl ethers, aspergillusethers B-D (3–5), were isolated from the soil-derived fungus Aspergillus unguis PSU-RSPG204 together with five known compounds including methyl orsellinate (6), pilobolusate (7), aspergillusphenol A (8), orcinol (9) and (+)-montagnitol (10). Their structures were established by spectroscopic evidence. Compound 8 showed moderate antibacterial activity against Staphylococcus aureus and methicillin-resistance S. aureus with MIC values of 16 and 8 μg/mL, respectively, whereas compound 5 exhibited moderate antifungal activity against Candida albicans (NCPF3153), flucytosine-resistant Cryptococcus neoformans (ATCC90113) and Penicillium marnefeii with the MIC values of 16, 8 and 16 μg/mL, respectively. For cytotoxic activity, compound 7 showed strong activity against the human oral carcinoma (KB) cell lines with an IC50 value of 4.57 μM. In addition, all of them were inactive against African green monkey kidney fibroblast cells.

Chemical Composition of Umbilicaria crustulosa and U. cylindrica

The chemical composition of ether, ethyl acetate and dichloromethane extracts of Umbilicaria crustulosa and U. cylindrica were determined for the first time by HPLC-UV, GC-FID and GC-MS. The HPLC-UV analysis was revealed the presence of methyl orsellinate, lecanoric acid, crustinic acid, gyrophoric acid and atranorin in U. crustulosa extracts while in U. cylindrica extracts were detected following compounds: salazinic acid, norstictic acid, atraric acid, gyrophoric acid and atranorin. GC-FID and GC-MS analysis were enabled the identification of orsellinic acid (40.4%) and orcinol (48.1%) as main components of U. crustulosa extracts and atraric acid (8.5%) and orcinol (10.3%) in U. cylindrica extracts.