Synthesis and evaluation of esters obtained from phenols and phenoxyacetic acid with significant phytotoxic and cytogenotoxic activities.

There is a growing demand for herbicides that are more effective than conventional ones yet less harmful to ecosystems. In light of this, this study aimed to synthesize esters from phenols and phenoxyacetic acid, using compounds with known phytotoxic potential as starting materials. Phenoxyacetic acid was first synthesized and then utilized in the synthesis of seven esters through Steglich esterification, employing N,N'-dicyclohexylcarboimide and N,N-dimethylpyridin-4-amine in the presence of phenols (thymol, vanillin, eugenol, carvacrol, guaiacol, p-cresol, and ß-naphthol), yielding esters 1-7. All synthesized compounds were characterized using mass spectrometry, 1H, and 13C NMR. These compounds were tested for phytotoxicity to evaluate their effects on the germination and root development of Sorghum bicolor and Lactuca sativa seeds, and for the induction of alterations in the mitotic cycle of meristematic cells of L. sativa roots. Esters 1, 3, 4, and 5 exhibited the most significant phytotoxic activity in both L. sativa and S. bicolor. Alterations in the mitotic index and frequency of chromosomal alterations in L. sativa roots revealed the cytotoxic, genotoxic effects, and the aneugenic mode of action of the tested molecules. These findings suggest that these compounds could serve as inspiration for the synthesis of new semi-synthetic herbicides.

Characterization and quantification of peptaibol produced by novel Trichoderma spp: Harnessing their potential to mitigate moisture stress through enhanced biochemical and physiological responses in black pepper (Piper nigrum L.).

Trichoderma spp. is primarily applied to manage biotic stresses in plants. Still, they also can mitigate abiotic stresses by the stimulation of antioxidative protective mechanisms and enhanced synthesis of secondary metabolites. The study optimized the conditions to enhance peptaibol production by novel Trichoderma spp, characterized and quantified peptaibol- alamethicin using HPLC and LC MS-MS. The present study investigated these isolates efficacy in enhancing growth and the associated physio-biochemical changes in black pepper plants under moisture stress. Under in vitro conditions, out of 51 isolates studied, six isolates viz., T. asperellum (IISR NAIMCC 0049), T. erinaceum (IISR APT1), T. harzianum (IISR APT2), T. harzianum (IISR KL3), T. lixii (IISR KA15) and T. asperellum (IISR TN3) showed tolerance to low moisture levels (5, 10 and 20%) and higher temperatures (35 and 40 °C). In vivo evaluation on black pepper plants maintained under four different moisture levels (Field capacity [FC]; 75%, 50%, and 25%) showed that the plants inoculated with Trichoderma accumulated greater quantities of secondary metabolites viz., proline, phenols, MDA and soluble proteins at low moisture levels (50% and 25% FC). In the present study, plants inoculated with T. asperellum and T. harzianum showed significantly increased growth compared to uninoculated plants. The shortlisted Trichoderma isolates exhibited differences in peptaibol production and indicated that the peptide might be the key factor for their efficiency as biocontrol agents. The present study also demonstrated that Trichoderma isolates T. harzianum and T. asperellum (IISR APT2 & NAIMCC 0049) enhanced the drought-tolerant capabilities of black pepper by improving plant growth and secondary metabolite production.

Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal's potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention. METHODS: To simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC's therapeutic effects on chondrocytes. RESULTS: The results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1ß, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA. CONCLUSIONS: This study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC's comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC's therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.

Cytotoxic activity of callus extract from Vachellia farnesiana (L) Wight & Arn.

The in vitro cultures of Vachellia farnesiana (L) Wight & Arn. have demonstrated cytotoxic activity through callus extract on the HeLa cell line. Explants excised from in vitro-grown seedlings from seeds of two different locations were inoculated on Murashige and Skoog (MS) culture media containing various concentrations of N-6 benzyladenine (BA) or kinetin with 2,4-dichlorophenoxyacetic acid (2,4-D). Optimal efficiency in friable callus induction (100%) was achieved in leaf explants cultured on MS media containing 2.32 µM BA + 13.57 µM 2,4-D. Plant tissues (callus and leaf) were extracted and subjected to quantitative phytochemical analysis, revealing the highest total alkaloid and phenolic content in leaf extracts from Queretaro adult specimens (339.5 ± 20.9 mg atropine equivalents (AE) per g dry extract (DE) and 158.4 ± 12.5 mg gallic acid equivalents (GAE) per g DE, respectively). In contrast, callus cultures exhibited significantly higher total triterpene content (356-381 mg ursolic acid equivalents (UAE) per g DE) compared to leaf extracts (208-243 mg UAE/g DE). Both leaf and callus extracts displayed cytotoxic activity against the HeLa cell line, with a significantly lower half-maximal inhibitory concentration (IC50) for leaf extracts (28-32 µg/mL) compared to callus cultures (43-66 µg/mL), suggesting that alkaloids were primarily responsible for the cytotoxic activity. Furthermore, this study provides valuable insights into the controlled production of bioactive compounds with cytotoxic activity, with callus serving as a rich source.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

Proton vs Electron: The Dual Role of Redox-Inactive Metal Ions in Permanganate Oxidation Kinetics.

Redox-inactive metal-ion-driven modulation of the oxidation behavior of high-valent metal-oxo complex has garnered significant interest in biological and chemical synthesis; however, their role in permanganate (Mn(VII)) oxidation for the removal of organic pollutants has been largely neglected. Here, we uncover the impact of six metal ions (i.e., Ca2+, Mg2+, Ni2+, Zn2+, Al3+, and Sc3+) presenting in water environments on Mn(VII) activity. These ions uniformly boost the electron and oxygen transfer capabilities of Mn(VII) while impeding proton transfer, as evidenced by electrochemical tests, thioanisole probe analysis, and the kinetic isotope effect. The observed effects are intricately linked to the Lewis acidity of the metal ions. Further mechanistic insights reveal that Mn(VII) can interact with metal ions without direct reduction. Such interactions modify the electronic configuration of Mn(VII) and create an acidic microenvironment, thus increasing its electrophilicity and the energy barrier for the abstraction of proton from organic substrates. More importantly, the efficacy of Mn(VII) in removing phenolic pollutants is regulated by these ions through changing the driving force for proton and electron transfer, i.e., facilitated at pH > 4.5 and inhibited at lower pH. The contribution of active Mn intermediates is also discussed to reveal the oxidative mechanism of the metal ion/Mn(VII) system. These findings not only facilitate the rational design of Mn(VII) oxidation conditions in the presence of metal ions for water decontamination but also offer an alternative paradigm for enhancing electrophilic oxidation.

Xeroderris stuhlmannii (Taub.) Mendonça & E.P.Sousa (Fabaceae): Evidence of the antihypertensive and antioxidant activities of its leaf aqueous extract in cadmium chloride hypertensive rats.

Xeroderris stuhlmannii (Fabaceae) is a medicinal reported in Cameroonian herbal medicine to treat hypertension. The aim of the study was to assess the antihypertensive and antioxidant activities of X. stuhlmannii aqueous leaf extract (AEXS) on cadmium chloride-induced hypertensive rats. The in vitro antioxidant activities of AEXS were investigated for their radical scavenging potency using 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric reducing antioxidant power (FRAP), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), Nitric oxide (NO) and OH- assays completed with oxidative stress markers analyses. Antihypertensive activity of AEXS (35, 100, and 300 mg/kg) was assessed in CdCl2 induced-hypertensive rats. Antihypertensive activities performed include systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) variation, followed by evaluation of selected biochemical parameters in urine, blood (Alanine aminotransferase (ALT), aspartate aminotransferase (AST)), creatinine, urea and total protein) and histological examination of tissue samples (aorta, heart, kidneys and liver). The amount of the phenols of the leaf extract was estimated in mg gallic acid equivalent and identification of some compounds was done by UPLC-UV-ESI-TOF-MS. Accordingly, the identified phenols were stuhlmannione A (1), formononetin (2), stuhlmarotenoid A (3), 9-methoxymaackiain (4), 4-hydroxymaackiain (5) and 7-hydroxy-3',4'-methylenedioxy-isoflavone (6). The extract exhibited a significant (P < 0.05-0.001) decrease of SBP, DBP and HR when compare to control. AEXS also reduced (P < 0.05) serum rates of ALT, AST, and urea. The extract showed beneficial effects on alterations observed in the histological structures of the aorta, heart, kidneys and liver. AEXS highlighted high level of phenols (26.48 ± 2.89 mg GAE/g) and a strong antiradical activity on DPPH, ABTS+, OH- and NO with IC50 of 148.8 µg/mL, 27.83 µg/mL, 22.29 µg/mL, 29.84 µg/mL respectively. An optical density of 1.79 nm was obtained with FRAP test. Thus, X. stuhlmannii leaf extract has in vitro antioxidant and antihypertensive effects that may support its use against hypertension.

Contribution of distinct components in divergent organic amendments to long-term accumulation of soil organic matter in agricultural soils: evidence from thermally assisted hydrolysis and methylation-GC/MS.

Although maintaining/improving soil organic matter (SOM) quantity through utilizing organic amendments (OAs) is a productive practice, information on OA components contributing to long-term SOM accumulation in agricultural soils remains meager. Hence, we examined soil samples from a long-term experiment with different fertilizer managements, including no fertilizer (NF), chemical fertilizer (CF) only (CF), bark compost plus CF (BC + CF), coffee residue compost plus CF (CRC + CF), cattle manure compost plus CF (CMC + CF), and cattle manure compost (CMC) or sewage sludge compost (SSC) alone at a higher application rate. SOM in those samples was physically fractionated into free particulate form (fSOM), free form occluded in aggregates (oSOM), weakly bound form (wSOM), and strongly bound form (sSOM). Analysis of structural components in OAs and SOM fractions using thermally assisted hydrolysis and methylation combined with gas chromatography/mass spectrometry (THM-GC/MS) revealed OA components that have contributed to long-term SOM accumulation in each treatment. The SSC was characterized by higher proportions of short-chain fatty acids (FAs; 50%) and other aliphatic compounds (22%). Correlation analysis suggested that these characteristics may be effective for greater C accumulation in the bulk soil and wSOM fraction. The proportion of lignin-derived phenols, e.g., 3,4-dimethoxybenzaldehyde (Vh) and 1,2-dimethoxy-4-(1,2,3-trimethoxypropyl)benzene, was high in CMC (43%), presumably vital for promoting C accumulations in the oSOM, wSOM, and sSOM fractions in the CMC treatment. The short-chain FAs in CRC and aromatic components in BC are likely important for contributing fSOM accumulation.

Associations between single and combined exposures to environmental phenols and ulcerative colitis in American adults.

OBJECTIVE: The etiology of ulcerative colitis (UC) is complex and involves multiple factors, with exposure to environmental toxins potentially contributing greatly to its pathogenesis. Therefore, this study was carried out with the purpose of delving into the associations between single and combined exposures to environmental phenols and UC among American adults. METHODS: Survey data from the 2009-2010 National Health and Nutrition Examination Survey were selected for our research. The associations between single and combined exposures to environmental phenols and the prevalence of UC were analyzed using weighted multivariate logistic regression models as well as Bayesian kernel machine regression (BKMR). RESULTS: A total of 1,422 adults aged 20 years old and above were included in this study, 17 of whom had UC. The correlation matrix showed strong associations between 2,4-dichlorophenol (2,4-DCP) and 2,5-dichlorophenol (2,5-DCP) (R = 0.81), as well as between 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol (2,4,6-TCP) (R = 0.73). The logistic regression model revealed that, after adjusting for confounders, exposure to environmental phenols was positively associated with the prevalence of UC, with 2,4,6-TCP showing a significant association (OR = 2.37, 95 % CI = 1.10, 5.09, P = 0.037). The BKMR analysis indicated an upward trend in the overall effect of combined exposures to environmental phenols on UC. All five phenols contributed to this effect, with 2,4,6-TCP exhibiting the most pronounced effect. When other compounds were fixed at the 50th percentile, the impact of the five phenols on UC demonstrated a positive association, without any noteworthy interaction among the compounds. CONCLUSION: Our findings suggested that exposure to environmental phenols may contribute to the occurrence of UC among American adults.

Rapid aqueous-phase dark reaction of phenols with nitrosonium ions: Novel mechanism for atmospheric nitrosation and nitration at low pH.

Dark aqueous-phase reactions involving the nitrosation and nitration of aromatic organic compounds play a significant role in the production of light-absorbing organic carbon in the atmosphere. This process constitutes a crucial aspect of tropospheric chemistry and has attracted growing research interest, particularly in understanding the mechanisms governing nighttime reactions between phenols and nitrogen oxides. In this study, we present new findings concerning the rapid dark reactions between phenols containing electron-donating groups and inorganic nitrite in acidic aqueous solutions with pH levels <3.5. This reaction generates a substantial amount of nitroso- and nitro-substituted phenolic compounds, known for their light-absorbing properties and toxicity. In experiments utilizing various substituted phenols, we demonstrate that their reaction rates with nitrite depend on the electron cloud density of the benzene ring, indicative of an electrophilic substitution reaction mechanism. Control experiments and theoretical calculations indicate that the nitrosonium ion (NO+) is the reactive nitrogen species responsible for undergoing electrophilic reactions with phenolate anions, leading to the formation of nitroso-substituted phenolic compounds. These compounds then undergo partial oxidation to form nitro-substituted phenols through reactions with nitrous acid (HONO) or other oxidants like oxygen. Our findings unveil a novel mechanism for swift atmospheric nitrosation and nitration reactions that occur within acidic cloud droplets or aerosol water, providing valuable insights into the rapid nocturnal formation of nitrogen-containing organic compounds with significant implications for climate dynamics and human health.