Β-resorcylic Acid Research Articles

β-resorcylic acid released by Limosilactobacillus reuteri protects against cisplatin-induced ovarian toxicity and infertility

Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, β-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L.reuteri or β-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, β-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that β-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.

Oral β-RA induces metabolic rewiring leading to the rescue of diet-induced obesity

Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as β-resorcylic acid (β-RA). Here, we show that oral supplementation with β-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of β-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of β-RA. Consequently, β-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of β-RA supports its translational potential. Thus, β-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).

Role of marination, natural antimicrobial compounds, and packaging on microbiota during storage of chicken tawook

The aim of this study was to investigate the antimicrobial effect of marination, natural antimicrobials, and packaging on the microbial population of chicken tawook during storage at 4°C. Chicken meat was cut into 10 g cubes and marinated. The chicken was then mixed individually with 0.5% or 1% (w/v) vanillin (VA), β-resorcylic acid (BR), or eugenol (EU), and stored under aerobic (AP) or vacuum (VP) packing at 4°C for 7 d. The marinade decreased microbial growth as monitored by total plate count, yeast and mould, lactic acid bacteria, and Pseudomonas spp. by about 1 log cfu/g under AP. The combination of marinade and antimicrobials under AP and VP decreased growth of spoilage-causing microorganisms by 1.5 – 4.8 and 2.3 – 4.6 log cfu/g, respectively. Change in pH in VP meat was less than 0.5 in all treated samples including the control. Marination decreased the lightness of the meat (L*) and significantly (p < 0.05) increased the redness (A*) and yellowness (B*). Overall acceptability was highest for marinated samples with 0.5% BR.

Total synthesis of 14-membered ring β-resorcylic acid lactone (+)-monocillin II.

This study outlines the total synthesis of (+)-monocillin II, wherein a cis-isomer selectively produces a trans-isomer during the ring-closing metathesis. The Mitsunobu reaction conducted at -60 °C, facilitating the formation of an ester bond, was the key to completing the total synthesis, which was accomplished in the longest linear sequence of 10 steps with an overall yield of 9.3%.

Preservative effect of pomegranate-based marination with β-resorcylic acid and cinnamaldehyde on the microbial quality of chicken liver

Chicken liver is considered a delicacy in the Middle East where pomegranate molass is commonly used as a salad dressing and in marinade recipes. Marinated chicken liver is a common entrée and represents a value-added product compared to the otherwise unmarinated liver which commands a lower price. The aim of this study was to investigate the inhibitory effects of a pomegranate-based marinade alone or following the addition of cinnamaldehyde or β-resorcylic acid on the spoilage microorganisms present in chicken liver during storage for 14 d at 4°C or under mild temperature abuse conditions (10°C). The pH and microbial populations of total plate count (TPC), lactic acid bacteria (LAB), Pseudomonas spp. (PS), yeast and mold (YM), and Enterobacteriaceae (EN) were tested during the storage period and the shelf life was determined (defined as 107 log cfu/g). Sensory analysis was also conducted. The pH increased by a greater extent in unmarinated samples as compared to marinated samples (with or without antimicrobials) upon storage. The initial TPC, LAB, PS, YM, and EN microbial populations in the chicken liver were 3.85 ± 0.79, 3.73 ± 0.85, 3.85 ± 0.79, 3.73 ± 0.87, and 3.69 ± 0.23 log cfu/g, respectively. The marinade decreased the microbial populations by 2 to 4 log cfu/g. The marinade and antimicrobial mixture decreased the microbial populations by 3 to 4 log cfu/g. Except for 1 sample, none of the marinated chicken liver samples with or without antimicrobials reached the end of shelf life even up to 14 d of storage at both 4°C and 10°C. The overall sensory score was rated around 6/9 for the treated samples.

Effect of plant-derived antimicrobials, eugenol, carvacrol, and β-resorcylic acid against Salmonella on organic chicken wings and carcasses

Organic poultry constitutes a sizeable segment of the American organic commodities market. However, processors have limited strategies that are safe, effective, and approved for improving the microbiological safety of products. In this study, the efficacy of 3 plant-derived antimicrobials (PDAs), eugenol (EG), carvacrol (CR), and β-resorcylic acid (BR) was evaluated against Salmonella on organic chicken wings and carcasses. Wings inoculated with Salmonella (6 log10 CFU/wing) were treated with or without the treatments (BR [0.5%, 1% w/v], EG [0.5%, 1% v/v], CR [0.5%, 1% v/v], chlorine [CL; 200 ppm v/v], or peracetic acid [PA; 200 ppm v/v]) applied for 2 min at 54°C (scalding study) or 30 min at 4°C (chilling study). Homogenates and treatment water were evaluated for surviving Salmonella. Six wings or carcasses per treatment were analyzed in each study. All treatments, except CL and 0.5% BR in the scalding study, yielded significant reductions of Salmonella on wings compared to the positive control (PC-Salmonella inoculated samples not treated with antimicrobials). To follow, carcasses inoculated with Salmonella (higher inoculum [106 CFU/carcass] or lower inoculum [104 CFU/carcass]) and immersed in antimicrobials (CR 1% [v/v] and industry controls [CL {200 ppm}, or PA [200 ppm]) for 30 min at 4°C were stored until analysis. For the higher inoculum study, 1% CR resulted in a 3.9 log10 CFU/g reduction of Salmonella on the carcass on d 0 compared to PC (P < 0.05); however, CL yielded no reduction. On d 3, CR and PA resulted in 0.9 and 1.2 log10 CFU/g reduction of Salmonella, respectively (P < 0.05). For the lower inoculum study, consistent Salmonella reductions were obtained with CR and PA (1.4-2.1 log10 CFU/g) on d 0 and 7. High reductions of Salmonella in processing water were obtained in all studies. CR effectively controls Salmonella on wings and carcasses and in processing water immediately after application. Follow-up studies on the organoleptic characteristics of PDA-treated chicken carcasses are necessary.

A Critical Assessment of Extraction Methodologies for the Valorization of Agricultural Wastes: Polyphenolic Profile and Bioactivity

Different extraction techniques were used to exploit fruit processing residues for their use as a source of phenolic compounds. Three different extraction methods, namely microwave-assisted extraction (MAE), subcritical water extraction (SWE), and maceration (M), were assessed to gauge their respective efficacies. Total phenolic content (TPC) and total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), and radical scavenging activity ABTS assay were evaluated. High-performance liquid chromatography was used to assess the polyphenolic profile. MAE was the extraction technique that allowed the highest recovery of polyphenolic compounds. Concerning the fruit by-products analyzed, the extract of pomegranate peels obtained using M60C and MAE had the highest TPC (313 ± 24 mg GAE/g dry weight (dw)) and TFC (36.0 ± 2.8 mg EE/g dw), respectively, and the highest antioxidant activity (FRAP = 740 ± 67 mg AAE/g dw and ABTS (628 ± 27 mg TE/g dw) corresponded to M60C. The phenolic composition obtained for this sample using high-performance liquid chromatographic–diode array detection (HPLC–DAD) showed that gallic acid, protocatechuic acid, β-resorcylic acid, (+)-cathechin, and rutin were the main phenolics found. The findings underscore the capacity of agricultural by-products to act as a source of phenolic compounds. This offers a feasible solution to enhance the nutritional content in food while simultaneously minimizing environmental waste.

In Ukrainian

Aromatic organic acids are among the common environmental pollutants that enter the water with washouts from agricultural lands, wastewater from chemical and pharmaceutical industries. Taking into account the high toxicity of aromatic substances, the important task of water purification is the removal of their trace amounts. This problem can be solved by using chemically modified inorganic materials, such as silicas, which have high mechanical, chemical, hydrolytic, and radiation stability. Therefore, they do not lose their sorption capacity during long-term use and do not pollute water with sorbent degradation products. The purpose of this work is the synthesis of a sorption-active material for removal of toxic aromatic acids by chemical immobilization of β-cyclodextrin functional groups on an aerosilogel (highly dispersed type of amorphous silica). A β-cyclodextrin-containing aerosilogel was synthesized by two-stage liquid-phase chemical modification of hydroxylated silica surface. Using the methods of IR spectroscopy, spectrophotometry, thermogravimetry, pH metry, low-temperature adsorption-desorption of nitrogen, chemical and elemental analysis of the surface, the surface structure and its quantitative chemical composition, and also parameters of porous structure of initial and chemically modified aerosilogels were determined. Sorption of benzoic, salicylic and β-resorcylic acids on aerosilogels from aqueous buffer solutions with pH=1 was studied. The insignificant contribution of silanol and aminopropyl groups and complete participation of chemically fixed β-cyclodextrin in the sorption of aromatic acids were proved. The results obtained are analyzed using kinetic models for pseudo-first and pseudo-second order processes, as well as Langmuir and Freundlich models for equilibrium adsorption on homogeneous and heterogeneous surfaces. It has been found that the sorption kinetic processes are well described by a pseudo-first order equation (in the presence of one type of functional groups on the surface) and a pseudo-second order equation for bi- and trifunctional aerosilogels. Experimental results on the equilibrium sorption of aromatic acids on β-cyclodextrin-containing aerosilogel are in good agreement with the Langmuir adsorption equation. This is evidence of decisive contribution of grafted oligosaccharide groups to the sorption of organic acids. The proposed chemical approach to increasing the sorption activity of aerosilogel can be used to obtain specific chromatographic carriers, as well as inorganic sorbents for the effective removal of small amounts of highly toxic organic substances from water and aqueous solutions.

New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus Penicillium antarcticum KMM 4685.

Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (1), β-resoantarctines A-C (3, 5, 6) and 8-dehydro-β-resoantarctine A (4), together with known 14-hydroxyasperentin (5'-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher's method, and the biogenetic pathways for compounds 3-6 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 3-6 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds 3, 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.

Biophysical and molecular modelling analysis of the binding of β-resorcylic acid with bovine serum albumin

The bovine serum albumin (BSA) is a model carrier protein that transports and deposits the various endogenous and exogenous ligands in the body. β-resorcylic acid (BR) is a phyto-phenolic molecule mainly used in the food industry because of its antibacterial, flavouring and preservative nature. The interactions of small ligand molecules with proteins are of great importance for researchers from the pharmacology perspective. This article explains the mechanism of binding of BR with BSA with the help of multi-spectroscopic approaches and molecular modelling. The UV absorption and fluorescence spectroscopy affirmed the formation of BSA-BR complex. The thermodynamic studies confirmed the nature of the reaction to be spontaneous and exothermic, and the stabilisation of the complex by van der Waals interactions and hydrogen bonding. The energy transfer was found to occur with a high probability. BR induced the microenvironmental and conformational alterations BSA as revealed by synchronous spectra, 3D fluorescence maps, circular dichroism (CD), resonance-enhanced Rayleigh scattering (RRS), red edge excitation shift ( REES) and Fourier transform infrared (FT-IR). The β-cyclodextrin (β-cd), metals and vitamins largely influenced the BR-BSA binding strength. Competitive displacement assays further elucidated the BR binds to BSA at subdomain IIIA (site II). Molecular docking and simulations computationally validated the results of the wet lab experiments. • The BSA-BR complex was affirmed with 1:1 binding stoichiometry and quenching in static mode. • The binding reaction was spontaneous and exothermic, involving van der Waals forces and hydrogen bonding. • The binding strength was found to change in the presence of metal ions, vitamins and β-cd. • BR binds with BSA near subdomain IIIA (site II). • BR induced minor changes in the conformation and microenvironment in BSA.

New Anti-Inflammatory β-Resorcylic Acid Lactones Derived from an Endophytic Fungus, Colletotrichum sp.

The endophytic fungus Colletotrichum gloeosprioides JS0419, isolated from the leaves of the halophyte Suaeda japonica, produced four new β-resorcylic acid derivatives, colletogloeopyrones A and B (1 and 2) and colletogloeolactones A and B (3 and 4), and seven known β-resorcylic acid lactones (RALs). The structures of these compounds were elucidated via analysis of the high-resolution mass spectrometry and nuclear magnetic resonance data. Compounds 1 and 2 showed a dihydrobenzopyranone ring with a linear C9 side chain, which is rarely observed in RALs. All isolated compounds were evaluated for their anti-inflammatory activities. Colletogloeopyrone A (1), monocillin II (5), and monocillin II glycoside (6) were effective in reducing nitric oxide production without cytotoxicity. They also inhibited the secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as demonstrated by the expression of mRNA corresponding to IL-6 and TNF-α. Mechanistically, compounds 5 and 6 significantly inhibited the protein expression of nuclear factor-κB, IκBα, IKKα/β, inducible nitric oxide synthase, and cyclooxygenase (COX)-2, whereas compound 1 only inhibited COX-2 expression. This study indicated that RAL-type compounds 1, 5, and 6 demonstrated potential anti-inflammatory activity by inhibiting the synthesis of pro-inflammatory cytokines.

Effect of Eugenol, Vanillin, and β-Resorcylic Acid on Foodborne Pathogen Survival in Marinated Camel Meat

The combined inhibitory effect of essential oils (EOs) with meat-based marinades has not been fully studied. Therefore, the present study aimed to gauge the effect of a yogurt-based marinade when individually combined with three EOs, namely eugenol (EU), vanillin (VA), or β-resorcylic acid (BR) on camel meat cubes inoculated with Listeria monocytogenes, Salmonella spp., and Escherichia coli O157:H7 during storage. Fresh camel meat cubes of 10 g were inoculated with bacteria and dipped in the mixture of marinade and EO. Overall, the study had six EO treatments (EU 0.5%, EU 1%, VA 0.5%, VA 1%, BR 0.5%, and BR 1%) and two controls (meat without marinade and marinated meat). Treated meat cubes were stored at 4°C or 10°C for 1, 4, and 7 d. Adding only marinade to the camel meat at 10°C decreased the pathogens by 0.8–2.4 log CFU/g. At 10°C, BR decreased L. monocytogenes, E. coli O157:H7, and Salmonella spp. by 2.0, 1.5, and 1.3 log CFU/g, while EU caused a decrease (p < 0.05) of 1.9, 1.2, and 0.9 log CFU/g, respectively. Similarly, VA caused a reduction in these microorganisms of 1.3, 1.1, and 1.0 log CFU/g, respectively (p < 0.05). The combination of marinade and EO resulted in a decrease of the pathogens ranging from 0.9–1.4 and 2.8–3.7 log CFU/g at 4 and 10°C, respectively. The antimicrobial efficacy of EO alone or when combined with marinade was higher at 10°C than at 4°C with all three pathogens at both 0.5% and 1%. Overall, EOs were found to enhance the microbial safety of camel meat. In addition, they are antimicrobials that occur naturally, require a minimum investment, and may prove to be a great asset for marinated camel meat producers.

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

Defects in Coenzyme Q (CoQ) metabolism have been associated with primary mitochondrial disorders, neurodegenerative diseases and metabolic conditions. The consequences of CoQ deficiency have not been fully addressed, and effective treatment remains challenging. Here, we use mice with primary CoQ deficiency (Coq9R239X), and we demonstrate that CoQ deficiency profoundly alters the Q-junction, leading to extensive changes in the mitochondrial proteome and metabolism in the kidneys and, to a lesser extent, in the brain. CoQ deficiency also induces reactive gliosis, which mediates a neuroinflammatory response, both of which lead to an encephalopathic phenotype. Importantly, treatment with either vanillic acid (VA) or β-resorcylic acid (β-RA), two analogs of the natural precursor for CoQ biosynthesis, partially restores CoQ metabolism, particularly in the kidneys, and induces profound normalization of the mitochondrial proteome and metabolism, ultimately leading to reductions in gliosis, neuroinflammation and spongiosis and, consequently, reversing the phenotype. Together, these results provide key mechanistic insights into defects in CoQ metabolism and identify potential disease biomarkers. Furthermore, our findings clearly indicate that the use of analogs of the CoQ biosynthetic precursor is a promising alternative therapy for primary CoQ deficiency and has potential for use in the treatment of more common neurodegenerative and metabolic diseases that are associated with secondary CoQ deficiency.

Rare β-Resorcylic Acid Derivatives from a Halophyte-Associated Fungus Colletotrichum gloeosporioides JS0419 and Their Antifungal Activities.

Six new β-resorcylic acid derivatives (1–5 and 7) were isolated from a halophyte-associated fungus, Colletotrichum gloeosporioides JS0419, together with four previously reported β-resorcylic acid lactones (RALs). The relative and absolute stereochemistry of 1 was completely established by a combination of spectroscopic data and chemical reactions. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR data. Notably, compounds 1–3 had a β-resorcylic acid harboring a long unesterified aliphatic side chain, whereas the long aliphatic chains were esterified to form macrolactones in 4–9. Among the isolated compounds, monocillin I and radicicol showed potent antifungal activities against Cryptococcus neoformans, comparable to clinically available antifungal agents and radicicol showed weak antifungal activity against Candida albicans. These findings provide insight into the chemical diversity of fungal RAL-type compounds and their pharmacological potential.

Deciphering the biomolecular interaction of β-resorcylic acid with human lysozyme: A biophysical and bioinformatics outlook

The binding mechanism between human lysozyme (Lyz) and β-resorcylic acid (BR) was systematically examined by various biophysical and computational techniques. The studies like ultraviolet absorbance and steady-state fluorescence confirmed the complex formation with binding constant in the order of 103 M−1. The mechanism of fluorescence quenching of Lyz was found to be static. The average binding distance between Lyz and BR was calculated by FRET as per Forster’s theory. The changes in conformation and microenvironment in the secondary structure of Lyz in the presence of BR were confirmed by techniques like synchronous, three-dimensional fluorescence spectroscopy, Red edge excitation shift (REES) and circular dichroism (CD). The different temperature-based fluorescence experiments highlighted that the reaction is spontaneous and exothermic in nature. The van der Waals and hydrogen bonding are the main contributing forces in the complex formation as is evident from the negative values of enthalpy (ΔH) and entropy (ΔS). Further, the results obtained from in vitro experiments were also reaffirmed by in silico molecular docking, predicting the active binding site of BR in Lyz. HOMO-LUMO energy gap in BR was estimated by density functional theory (DFT) studies. Moreover, the effects of β-cyclodextrin, metal ions, and vitamins on the binding of BR with Lyz were also studied.

β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight.

Primary mitochondrial diseases are caused by mutations in mitochondrial or nuclear genes, leading to the abnormal function of specific mitochondrial pathways. Mitochondrial dysfunction is also a secondary event in more common pathophysiological conditions, such as obesity and metabolic syndrome. In both cases, the improvement and management of mitochondrial homeostasis remain challenging. Here, we show that beta-resorcylic acid (β-RA), which is a natural phenolic compound, competed in vivo with 4-hydroxybenzoic acid, which is the natural precursor of coenzyme Q biosynthesis. This led to a decrease in demethoxyubiquinone, which is an intermediate metabolite of CoQ biosynthesis that is abnormally accumulated in Coq9R239X mice. As a consequence, β-RA rescued the phenotype of Coq9R239X mice, which is a model of primary mitochondrial encephalopathy. Moreover, we observed that long-term treatment with β-RA also reduced the size and content of the white adipose tissue (WAT) that is normally accumulated during aging in wild-type mice, leading to the prevention of hepatic steatosis and an increase in survival at the elderly stage of life. The reduction in WAT content was due to a decrease in adipogenesis, an adaptation of the mitochondrial proteome in the kidneys, and stimulation of glycolysis and acetyl-CoA metabolism. Therefore, our results demonstrate that β-RA acted through different cellular mechanisms, with effects on mitochondrial metabolism; as such, it may be used for the treatment of primary coenzyme Q deficiency, overweight, and hepatic steatosis.

Cussonia arborea Hochst (Araliaceae): Ethnobotany, Pharmacology and Phytochemistry

Background: C. arborea belonging to Araliaceae family is used traditionally to cure many alien diseases including gonorrhoeae infection, diarrhea, malaria, and diabetes mellitus. The plant has been examined on the basis of scientific in vitro and in vivo evaluations possessing the major pharmacological activities including antimicrobial, antibacterial, antihyperglycemic, antiplasmodial and anticancer properties.&#x0D; Aim of the study: In the present paper, we reported the isolation and characterization of secondary metabolites from the methanol extract of the stem bark of Cussonia arborea Hochst after a short review of the traditional and pharmacological studies done on this important medicinal plant.&#x0D; Materials and methods: MeOH extract of stem bark of C. arborea was suspended in water and successively extracted with EtOAc and n-BuOH. The EtOAc extract (18 g) was subjected to repeated column chromatography to yield seven (1-7) compounds. Their structures were determined by means of NMR, and published data.&#x0D; Results: The isolated compounds were identified as: protocatechuic acid (1), mixture of 3,23-dihydroxyolean-12-en-28-oic acid (2a) and 3,23-dihydroxyurs-12-en-28-oic acid (2b) in ratio 5/4, 3-O-β-D-xylopyranosylolean-12-en-28-oic acid (3), 3-O-α-L-arabinopyranosylolean-12-en-28-oic acid (4), β-resorcylic acid (5), mixture of 3-O-β-D-glucopyranosyl-23-hydroxyolean-12-en-28-oic acid (6a) and 3-O-β-D-glucopyranosyl-23-hydroxyurs-12-en-28-oic acid (6b) in ration 4/1, 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl-3β-hydroxyolean-12-en-28-oic acid (7). Compounds 3, 4, 5, 7, 2b and 6b are herein reported for the first time in this plant

Exploring the binding mechanism of β-resorcylic acid with calf thymus DNA: Insights from multi-spectroscopic, thermodynamic and bioinformatics approaches

β-resorcylic acid (BR) is a phytochemical which is widely used in the food industry as a flavouring agent and preservative. It has also been found to exhibit antibacterial action against several types of food-borne bacteria. DNA is the main molecular target for many small molecules of therapeutic importance. Hence, the interest is rapidly growing among the researchers to elucidate the interaction between small molecules and DNA. Thus, paving the way to design novel DNA-specific drugs. In this study, an attempt was made to examine the mechanism of binding of BR with calf thymus DNA (ctDNA) with the help of various experiments based on spectroscopy and in silico studies. The spectroscopic studies like UV absorption and fluorescence affirmed the complex formation between BR and ctDNA. The observed binding constant was in the order of 103 M−1 which is indicative of the groove binding mechanism. These findings were further verified by dye-displacement assay, potassium iodide quenching, urea denaturation assay, the study of the effect of ssDNA, circular dichroism and DNA thermal denaturing studies. Different temperature-based fluorescence and isothermal titration calorimetry (ITC) experiments were employed to evaluate thermodynamic parameters. The analysis of thermodynamic parameters supports the enthalpically driven, exothermic and spontaneous nature of the reaction between BR and ctDNA. The forces involved in the binding process were mainly found to be hydrogen bonding, van der Waals and hydrophobic interactions. The results obtained from the molecular docking and molecular dynamics (MD) simulation were consistent with the in vitro experiments, which support the groove binding mode of BR with ctDNA.

Phytotoxic β-resorcylic acid derivatives from the endophytic fungus Lasiodiplodia theobromae in the mangrove plant

• New β -resorcylic acid derivatives were isolated from an endophyte L . theobromae . • Absolute configuration was established using Mosher's ester analysis and chemical ECD calculations. • (3 S, 7 R )-17- O -methyl- de - O -methyllasiodiplodin showed growth inhibitory effects against D. ciliaris. Three new β -resorcylic acid derivatives, 1 – 3 , were obtained from the endophytic strain Lasiodiplodia theobromae GI-1005, which was isolated from the mangrove plant Rhizopora mucronata. The structures of new compounds together with five known compounds were elucidated by NMR and MS analyses, and chemical means. The isolated compounds were evaluated for phytotoxicity against Digitaria ciliaris (southern crabgrass) and Lactuca sativa (lettuce). Compound 1 showed growth inhibitory effects against D. ciliaris in a dose-dependent manner.

In Ukrainian

The encapsulation of medicinal substances in various polymers is a common way to increase their thermal, hydrolytic, and chemical stability. However, the bioavailability of the encapsulated drugs decreases. The solution to this important problem can be the preparation of nanocapsules of medicinal substances using complexing agents, for example, cyclodextrins. The purpose of this work is to study the possibility of encapsulation of benzoic, salicylic, and β-resorcylic acids using α- and β-cyclodextrins. The interaction of benzene carboxylic acids with cyclodextrins in aqueous solutions at 20–30 оС has been studied by spectrophotometry. The formation of complexes with a composition of 1:1 in the cyclodextrin – benzene carboxylic acid systems has been proven. The stability constants of the complexes and the main thermodynamic parameters of complex formation have been calculated. It has been shown that the nature of changes in the spectral characteristics of benzene carboxylic acids in the presence of cyclodextrins can be used to predict the possibility of aromatic organic compounds encapsulation. The determining role of the complementarity of geometric parameters of cyclodextrins and benzene carboxylic acids in the preparation of inclusion complexes with features of nanocapsules has been found. The prospects of using β-cyclodextrin for encapsulation of benzene carboxylic acids have been demonstrated. The complexes of β-cyclodextrin with benzene carboxylic acids were synthesized and studied by IR spectroscopy, X-ray analysis and derivatography. The formation of two types of complexes in the β-cyclodextrin – benzene carboxylic acid system was established. The first type of complexes is formed due to nonspecific interactions between the hydrophobic cavity of β-cyclodextrin and the benzene carboxylic acid molecule, the second type is due to specific interactions between the functional groups of molecules. Benzoic and salicylic acids form nanocapsules with β-cyclodextrin, and their hydrolytic and thermal stability increases. Complexes of the second type acquire the properties of a new compound: β-resorcylic acid loses its individuality, forming strong supramolecular structures with β-cyclodextrin.