Ferulic Acid Derivatives Research Articles

Investigating the impact of active PHBV films on the nutritional quality of minimally processed apples

The aim of the study was to study the effect of an active film, a blend of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with a derivative of ferulic acid known as bis-O-dihydroferuloyl-1,4-butanediol (BDF), on the quality decay kinetic of minimally processed apples. Due to its properties, BDF is a promising candidate to serve both as a non-toxic biobased plasticizer and as an active additive, simplifying formulation of active packaging. Molecular modelling studies were conducted to explore the interaction between polyphenol oxidase (PPO) and BDF molecule, with the aim of understanding the mechanism of inhibition. The apple slices packed in different treatments exhibited an increase in PPO activity; however, the samples packed in active films showed a significantly slower rate of PPO activity (P < 0.05). Almost 50% of the ascorbic acid content degraded in the control samples (4.95–4.97 mg/100 g fruit weight (FW)) at d7 compared with the samples packaged in BDF-releasing films (5.81–6.1 mg/100 g FW) in which the degradation was only 30%. Using molecular modelling, it was observed that BDF (−6.3 kcal/mol) exhibited a stronger interaction with PPO than catechol (−4.5 kcal/mol) in the met and oxy states. BDF-releasing films showed superior preservative potential over the control as BDF competitively inhibits the PPO active site due to π–π stacking between the aromatic cycle of the BDF molecule and the PHE259 and hydrogen bonding with the active site.

Popcorn quality parameters and nutritional properties of oily maize (Zea mays var. ‘Everta’) hybrids subjected to different thermal treatments

This research assessed the popcorn quality parameters and nutritional properties of 5 oily maize (Zea mays var. ‘Everta’) hybrids under several thermal treatments (hot air, microwave, and wet cooking). Grains contained 2.16–4.51 % crude fat and 11.08–12.94 % protein, displayed a similar amount of individual p-coumaric and ferulic acid derivatives (p > 0.05) (free: 3.61–40.53 μg/g; bound: 1621.75–1970.94 μg/g), and total phytosterols ranging from 8.76 to 13.17 μg/g. Hot air- and wet cooking-treated grains showed the highest expansion volume (121.5–133.1 mL), and there were no differences in yield and residual percentage (p < 0.05). PCA analysis clustered samples 1 and 3 as the most influential on bound phenolics, expansion time, yield, and popped grains weight, mostly under hot air and wet cooking treatments. Spearman's correlations outlined the potential of the grains' total and bound phenolics on popping quality (weight and expansion time: 0.50–0.90). Results suggested the oily hybrids' nutritional potential and suitability to produce high-quality popcorn.

Cinnamic Acid Derivatives: Recent Discoveries and Development Strategies for Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline and memory impairment. It is characterized by the accumulation of Amyloid-beta (Aβ) plaques, the abnormal phosphorylation of tau protein forming neurofibrillary tangles, and is often accompanied by neuroinflammation and oxidative stress, which contribute to neuronal loss and brain atrophy. At present, clinical anti-AD drugs are mostly single-target, improving the cognitive ability of AD patients, but failing to effectively slow down the progression of AD. Therefore, research on effective multi-target drugs for AD has become an urgent problem to address. The main derivatives of hydroxycinnamic acid, caffeic acid, and ferulic acid, are widely present in nature and have many pharmacological activities, such as antimicrobial, antioxidant, anti-inflammatory, neuroprotective, anti-Aβ deposition, and so on. The occurrence and development of AD are often accompanied by pathologies, such as oxidative stress, neuroinflammation, and Aβ deposition, suggesting that caffeic acid and ferulic acid can be used in the research on anti-AD drugs. Therefore, in this article, we have summarized the multi-target anti-AD derivatives based on caffeic acid and ferulic acid in recent years, and discussed the new design direction of cinnamic acid derivatives as backbone compounds. It is hoped that this review will provide some useful strategies for anti-AD drugs based on cinnamic acid derivatives.

Trolox, Ferulic, Sinapic, and Cinnamic Acid Derivatives of Proline and GABA with Antioxidant and/or Anti-Inflammatory Properties.

Degenerative conditions, such as neurodegenerative disorders (Alzheimer's disease (AD), Parkinson's disease (PD)) and cardiovascular diseases, are complex, multifactorial disorders whose pathophysiology has not been fully elucidated yet. As a result, the available treatment options cannot eliminate these diseases radically, but only alleviate the symptoms. Both inflammatory processes and oxidation are key factors in the development and evolution of neurodegeneration, while acetylcholinesterase inhibitors are the most used therapeutic options against AD. In this work, following the multi-targeting compound approach, we designed and synthesized a series of proline and gamma-aminobutyric acid (GABA) amides with various acidic moieties that possess an antioxidant and/or anti-inflammatory potency. Proline is the pharmacophore of nootropic drugs (e.g., piracetam) used for memory improvement, while GABA is the main inhibitory neurotransmitter in the central nervous system. The designed molecules were subjected to a preliminary screening of their bioactivity in antioxidant and anti-inflammatory assays, as well as against acetylcholinesterase. Most of the synthesized compounds could inhibit lipid peroxidation (IC50 as low as 8 μΜ) and oxidative protein glycation (inhibition of up to 48%) and reduce the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH). In addition, all of the compounds were moderate inhibitors of lipoxygenase (LOX) (up to 46% at 100 μΜ) and could decrease carrageenan-induced paw edema in rats by up to 55%. Finally, some of the compounds were moderate acetylcholinesterase inhibitors (IC50 as low as 219 μΜ). The results confirmed the design rationale, indicating that the compounds could be further optimized as multi-targeting molecules directed against degenerative conditions.

Synthesis and Bioactivity Study of Mannich Base Derivatives of Ferulic Acid as a Tyrosinase Inhibitor and Antioxidant

Synthesis and Bioactivity Study of Mannich Base Derivatives of Ferulic Acid as a Tyrosinase Inhibitor and Antioxidant

A systematic UHPLC Q-ToF MS approach for the characterization of bioactive compounds from freeze-dried red goji berries (L. barbarum L.) grown in Serbia: Phenolic compounds and phenylamides

The aim of this study was to identify and characterise different classes of bioactive compounds from freeze-dried red goji berries (RGB) grown in Serbia, using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC Q-ToF MS). In addition, this study aims to demonstrate the importance of applying the advanced UHPLC Q-ToF MS technique in the identification of various biocompounds. The analysis showed the presence of 28 phenolic compounds, 3 organic acids, and 26 phenylamides. The 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG) was identified by UHPLC Q-ToF MS and quantified by standardised UHPLC-DAD method. Most of the compounds detected were derivatives of caffeic acid and ferulic acid, followed by quercetin derivatives. Among the phenylamides, several glucosylated caffeoyl and/or dihydrocaffeoyl derivatives of spermidine and spermine were characterized, confirming their recent characterization. Some glycosylated/non-glycosylated putrescine derivatives and caffeoyl-dihydrocaffeoyl-feruloyl spermidines were identified in goji berriesfor the first time. Their tentative structures and fragmentations were proposed.

Synthesis, crystal and molecular structure, DFT and antifungal activity studies of (E)-2-(3-methoxy-4-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)styryl)-5-((2-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole

Ferulic acid derivatives containing the 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine have displayed a wide array of pharmacological properties of interest to both medicinal and agricultural chemistry. This study focused on the synthesis of a new compound, (E)-2-(3‑methoxy-4-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)styryl)-5-((2-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole, with a ferulic acid skeleton, was synthesized via acetylation, condensation, cyclization, etherification, and thioetherification reactions. The title compound underwent comprehensive characterization using a variety of analytical techniques to gain a thorough insight into its molecular structure and properties. The structural arrangement of the compound was validated through X-ray diffraction and density functional theory calculations, while further analysis uncovered important physical and chemical attributes like molecular electrostatic potential and vibrational absorption bands. Moreover, the antifungal efficacy of the synthesized compounds was assessed, indicating their possible application in agriculture. This research lays the groundwork for the creation of novel compounds with antifungal properties.

Molecular docking of ferulic acid analogue compounds against epidermal growth factor receptor as a potential therapy for breast cancer

Background: Triple-negative breast cancer (TNBC) accounted for 18.1% of the breast cancer cases that occurred in Indonesia until 2020. Epidermal growth factor receptor (EGFR) overexpression is found in at least 50% of TNBC cases. So far, it is necessary to find an anti-cancer compound that has the potential against TNBC-type breast cancer to achieve good health and well-being. Objective: Ferulic acid derivatives were designed to be active on EGFR in silico study. Methods: Molecular docking was performed using Auto Dock 1.5.7 and PyRx 0.8 software, and visualisation was observed using Discovery Studio. FA ligand and its four derivatives were docked into the receptor EGFR (PDB ID: 3W33). Results: It was found that ferulic acid derivatives have high potential as an anticancer through EGFR inhibition in TNBC-type breast cancer. 4-(4-methyl) benzoyloxy-3-methoxycinnamic acid had the best potential among other derivatives, which showed the lowest binding free energy of -8.81 kcal/mol and the smallest Ki of 352.65nM. Methyl substitution at the benzoyloxy increased ligand interaction with amino acids in EGFR by increasing hydrophobic π-alkyl, π-π and alkyl binding with amino acids. Conclusion: The 4-(4-methyl) benzoyloxy-3-methoxycinnamic acid was the most prospective compound as an EGFR inhibitor and predicted as the most potential compound against breast cancer.

Chemical constituents from Notopterygium incisum and their anti-neuroinflammatory activity

Phytochemical research on an extract of Notopterygium incisum yielded fifteen compounds (1–15), including four previously undescribed compounds (10−13). The structures of the unreported compounds were elucidated by spectroscopic and spectrometric data analysis such as 1D and 2D NMR, IR and HR-ESI-MS. Compounds 1–5 and 10–14 were isolated from N. incisum for the first time. 7S⁎,8R⁎-Phenethyl-(7-methoxy-8-isoeugenol)-ferulate (10), 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) are the undescribed ferulic acid derivatives. Additionly, the anti-neuroinflammatory effects of compounds were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. The pharmacological results showed that 6β,10β-epoxy-4α-hydroxy-guaiane (6), teuclatriol (7) and 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) inhibited the production and expression of nitric oxide (NO) in the LPS-induced BV2 cells in a concentration-dependent manner. Acorusnol (4), teucladiol (9), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) only inhibited the release of NO at concentration of 20 μM. Moreover, 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) reduced the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated BV2 cells. The results demonstrated 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) could be a potential anti-neuroinflammatory agent and is worthy of further study.

Feruloyl Glyceride Mitigates Tomato Postharvest Rot by Inhibiting Penicillium expansum Spore Germination and Enhancing Suberin Accumulation.

Postharvest rot, caused by Penicillium expansum, in tomatoes poses significant economic and health risks. Traditional control methods, such as the use of fungicides, raise concerns about pathogen resistance, food safety, and environmental impact. In search of sustainable alternatives, plant secondary metabolites, particularly phenolic compounds and their derivatives, have emerged as promising natural antimicrobials. Among these, feruloyl glyceride (FG), a water-soluble derivative of ferulic acid, stands out due to its antioxidant properties, antibacterial properties, and improved solubility. In this study, we provide evidence demonstrating FG is capable of inhibiting the spore germination of P. expansum and effectively reducing the incidence rate of Penicillium rot of tomatoes, without compromising quality. Electron microscopy observations combined with metabolite and transcriptomic analyses revealed that FG treatments resulted in enhanced suberin accumulation through promoting the expression of suberin synthesis related genes and, consequently, inhibited the growth and expansion of P. expansum on the fruits. This work sheds light on the mechanisms underlying FG's inhibitory effects, allowing its potential application as a natural and safe alternative to replace chemical fungicides for postharvest preservation.

Ferulic Acid Derivatives Ameliorate Intestine Barrier Destruction by Alleviating Inflammatory Responses in Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.

Synthesis, biological evaluation, and molecular docking of novel ferulic acid derivatives containing a 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

In this study, 24 novel ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine were designed and synthesized. Bioactivity assay showed that some of the target compounds exhibited moderate to good antifungal activity against Botryosphaeria dothidea BD), Phomopsis sp. (PS), Botrytis cinerea (BC), Fusarium spp. (FS), Fusarium graminearum (FG), and Colletotrichum sp. (CS). Especially, compound 6f demonstrated superior antifungal activity against Phomopsis sp., with an EC50 value of 12.64 μg mL-1, outperforming pyrimethanil (35.16 μg mL-1) and hymexazol (27.01 μg mL-1). Meanwhile, compound 6p showed strong antibacterial activity against X. axonopodis pv. citri (XAC) in vitro, with an inhibition ratio of 85.76%, which was higher than thiodiazole copper's 76.59% at 100 μg mL-1. Furthermore, molecular docking simulations elucidated that compound 6f engaged in hydrogen bonding with the succinate dehydrogenase (SDH) enzyme at SER-17, SER-39, ARG-14 and ARG-43 sites, clarifying its mode of action. This study highlights the potential of these novel ferulic acid derivatives as promising agents for controlling fungal and bacterial threats to plant health. To the best of our knowledge, this study represents the first report on the antifungal and antibacterial properties of ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

O-Alkyl derivatives of ferulic and syringic acid as lipophilic antioxidants: effect of the length of the alkyl chain on the improvement of the thermo-oxidative stability of sunflower oil.

Lipid oxidation is the major cause of the deterioration of fat-containing foods, especially those containing polyunsaturated fatty acids (PUFAs). Antioxidant additives of synthetic origin are added to matrices rich in PUFAs, such as sunflower oil (SO). However, there is controversy regarding their safety, and their low solubility in both water and fat has led to the search for new covalent modifications through lipophilicity. This work presents the synthesis of O-alkyl acid derivatives from ferulic and syringic acids and the study of their antioxidant capacity and effect on the thermoxidative degradation of SO. Antioxidant activities were evaluated by employing ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays in a concentration range of 10-100 µg mL-1. The IC50 values for DPPH scavenging activity ranged from 15.61-90.43 µg mL-1. The results of the FRAP assay for both O-alkyl ferulic (3a-f) and syringic (5a-f) series revealed a "cut-off" effect on antioxidant activity in carbon five (C5). Thermoxidation study of additives 3b-c and 5b-c showed a decrease in the slope of extinction coefficients K 232 and K 270 in comparison with SOcontrol. Furthermore, 3c presented higher antioxidant activity than 3b and 1, with a power to decrease the thiobarbituric acid reactive species (TBARS) 6 times higher than SOcontrol at 220 °C. Additives 5b-c exerted a protective effect on the thermoxidation of SO. The results suggest that increasing lipophilic and thermal properties of antioxidants through O-alkyl acid derivatization is an effective strategy for accessing lipophilic antioxidant additives with potential use in food matrices.

Exploitation of the multitarget role of new ferulic and gallic acid derivatives in oxidative stress-related Alzheimer's disease therapies: design, synthesis and bioevaluation.

Monoamine oxidases (MAOs) inhibitors could decrease reactive oxygen species (ROS) generation, enhance mono-aminergic neural transmission, and have major therapeutic benefits for the treatment of Alzheimer's disease (AD). Following the conjunction of ferulic acid (FA)/gallic acid (GA) with sulfonamide, alanine and 2-aminobenzothiazole, we planned to assess the radical scavenging and antioxidant properties of synthesized analogs by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. GA analog 28 was identified as the most potent antioxidant compound with IC50 values of 1.77 μM and 2.06 μM in DPPH and ABTS assays respectively. In the in vitro enzyme inhibition assays, synthesized derivative 23 emerged as a potent multitarget inhibitor of hMAO-B, eeAChE. COX-2 and 5-LOX with IC50 values of 0.037 μM, 0.071 μM, 14.3 μM and 0.59 μM, respectively. Moreover, selected compounds 23, 25, 26 and 28 displayed good to moderate inhibition of self-mediated amyloid β1-42 peptide aggregation. More importantly, compounds 23, 25, 28 and 29 showed no neurotoxicity on SH-SY5Y cells and also showed excellent neuroprotective effects against H2O2-induced SH-SY5Y cells. In the in vivo experiment, antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) were studied in the brain of male BALB/c mice at the dose of 5 mg kg-1. All the tested compounds, except 29, have shown good to in vivo antioxidant potential. Docking studies on 3D crystallographic structures of AChE and MAO-B showed significant interactions with catalytic amino acid residues. In conclusion, the current study showed that FA/GA derivatives could be further exploited for their multitarget role in oxidative stress-related AD therapies.

Design, synthesis and antitumor study of novel NO-type porphyrin–ferulic acid derivatives for chemotherapy and photodynamic therapy

NO-type porphyrin-ferulic acid derivatives were obtained by combining NO donor, ferulic acid, and porphyrin. It can realize the combined treatment of phototherapy and chemotherapy and effectively kill cancer cells.

An effective cryobanking approach preserving the genetic, physiological and phytochemical stability of Polyscias filicifolia Bailey hairy roots

Cryopreservation procedures can affect the physiological and genetic stability of stored samples, as well as their biosynthetic potential, which is particularly important for medicinal plants; as such, it is necessary to refine a number of factors to ensure the effective long-term storage of plant cells. The article describes an effective method of cryopreservation of Polyscias filicifolia hairy roots. Briefly, hairy roots were subjected to osmotic dehydration (OD) with or without subsequent air dehydration (AD; for three to six hours) for cryobanking in liquid nitrogen. After regeneration, genetic stability was assessed using Inter Simple Sequence Repeats (ISSRs) and Start Codon Targeted (SCoT) markers, together with nuclear DNA content, survival rate and biomass growth. In addition, chlorogenic (CGA) and oleanolic acid (OA) yields were determined using HPLC-UV-Vis, and the extract profiled by HPLC-PDA-ESI-HRMS, and the antioxidant potential of the treated root extracts was assessed. OD alone was found to be insufficient for cryopreservation; it was necessary to precede it with AD. The highest survival (93%), and biomass growth (up to 3-fold), were noted for roots subjected to OD preceded by six-hour AD; however, AD had a detrimental effect on the genetic stability of roots when applied for five or six hours. Longer dehydration times correlated with greater CGA biosynthesis. Further, CGA content was enhanced to 2.6 mg g−1 dry weight (DW) at six months post regeneration and 2.2 mg g−1 at 12 months. OA yield was not affected by the cryopreservation conditions. HPLC-PDA-ESI-HRMS analysis confirmed that the main component was CGA, accompanied by ferulic acid derivatives, 3,5-O-dicaffeoylquinic acid (isochlorogenic acid A) and 5-p-coumaroylquinic acid. Interestingly, the profile of biosynthesized compounds in the roots did not change during cultivation for up to 12 months. The highest antioxidant activity, determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) assay, was noted for the extract from the OD variant, which also demonstrated the highest total phenolic content. Our findings indicate that OD followed by four-hour AD provides the best protection for hairy root meristems with regard to genetic stability, reliable growth and secondary metabolite biosynthesis capabilities.

Eco-Friendly Cinnamic Acid Derivatives Containing Glycoside Scaffolds as Potential Antiviral Agents.

Natural products are a crucial source in the development of new eco-friendly antiviral agents to control plant viral diseases. In our previous studies, some ferulic acid derivatives with good antiviral activity were obtained as an immune activator. To continue the discovery of eco-friendly antiviral agents, different monosaccharides were introduced into cinnamic acid skeletons by an activity-based strategy to obtain a series of cinnamic acid derivatives containing glycoside scaffolds, and their antiviral activities against tobacco mosaic virus (TMV) and tomato spotted wilt virus (TSWV) were evaluated. Among them, compound 8d showed the greatest protective activities against TMV and TSWV, with the EC50 values of 128.5 and 236.8 μg mL-1, respectively, which were superior to those of ningnanmycin (238.5 and 315.7 μg mL-1, respectively). Moreover, compound 8d could significantly improve the defense enzyme activities of peroxidase, chitinase, and β-1,3-glucanase. Proteomic and transcriptome analyses indicated that compound 8d regulated gene transcription and protein expression levels involved in the defense response to resist virus infection. The present study revealed that compound 8d is a potential lead candidate for the development of novel, eco-friendly, and natural-product-based antiviral agents.

Ferulated Poly(vinyl alcohol) based hydrogels

New graft copolymers were prepared by reaction of poly (vinyl alcohol) (PVA) with mono-imidazolide or bis-imidazolide derivatives of ferulic acid (FA) with the formation of ester bonds. The obtained graft copolymers, thanks to the crosslinking capability of FA, formed in water strong gels as verified by rheological analyses. The resulting hydrogels were characterized to evaluate their applicability as wound dressing. In this perspective, their capability to absorb and retain a large amount of fluid without dissolving was verified by swelling kinetics and Moisture Vapour Transmission Rate measurements. Their stability towards mechanical solicitations was assessed by quantifying elasticity, compliance, stress-relaxation, and adhesivity properties. The analyses pointed out that hydrogel PVA-FA2-3 obtained by feruloylation of PVA with bis-imidazole derivative of ferulic acid using an acylation agent/polymer molar ratio 0.03/1 resulted the best candidate for the foreseen application.

Design, synthesis, characterization of ferulic acid and p-coumaric acid amide derivatives as an antibacterial/antioxidant agent

Ferulic acid and p-coumaric acid, cinnamic derivatives of phenolic acid, have antibacterial, prooxidant, and antioxidant effects. In this study ferulic acid and p-coumaric acid amide derivatives were investigated for their antibacterial and antioxidant properties are described in this communication. The most effective conjugates against B subtilis were 5b (IC50: 215 ​± ​1.3 ​μM) and 4d (IC50: 336 ​± ​2.7 ​μM) and against P. aeruginosa were 4b (IC50: 365 ​± ​2.8 ​μM) and 5b (IC50: 341 ​± ​3.6 ​μM), whereas the none of conjugates were more effective against E. coli than reference Kanamycin. Conjugates 5b was the most effective against B subtilis of all the synthesized conjugates, with IC50 values of (IC50: 215 ​± ​1.3 ​μM). The free radical scavenging capacity of each compound was determined using the DPPH and ABTS assays. Conjugates 4b (IC50: 53 ​± ​3.6 ​μM), 4c (IC50: 58 ​± ​1.3 ​μM), 4d (IC50: 57 ​± ​2.5 ​μM), 5b (IC50: 29 ​± ​1.5 ​μM) and 4a (IC50: 56 ​± ​4.3 ​μM) have greater antioxidant capacity than ferulic acid and ascorbic acid in the DPPH assay. Whereas in the ABTS assay, compounds 4b (IC50: 7 ​± ​1.8 ​μM), 5b (IC50: 5 ​± ​0.7 ​μM), 4a (IC50: 9 ​± ​3.2 ​μM), 4g (IC50: 7 ​± ​2.3 ​μM), and 5a (IC50: 8 ​± ​4.3 ​μM) showed more antioxidant activity than ferulic acid, p-coumaric acid and ascorbic acid. Thus, a large library of compounds derived from bile acid can be easily synthesized for extensive structure-activity relationship studies in order to identify the most appropriate antibacterial and antioxidant agents.

Structural insights into the molecular mechanisms of substrate recognition and hydrolysis by feruloyl esterase from Aspergillus sydowii

The depolymerization of lignocellulosic biomass is facilitated by feruloyl esterases (FAEs), which hydrolyze ester bonds between lignin and polysaccharides. Fungal FAEs belonging to subfamily (SF) 6 release precursors such as ferulic acid derivatives, attractive for biochemical production. Among these, Aspergillus sydowii FAE (AsFaeE), an SF6 FAE, exhibits remarkable activity across various substrates. In this study, we conducted X-ray crystallography and kinetic analysis to unravel the molecular mechanisms governing substrate recognition and catalysis by AsFaeE. AsFaeE exhibits a typical α/β-hydrolase fold, characterized by a catalytic triad of serine, aspartate, and histidine. Comparative analysis of substrate-free, ferulic acid-bound, and sinapic acid-bound forms of AsFaeE suggests a conformational change in the loop covering the substrate-binding pocket upon binding. Notably, Pro158 and Phe159 within this loop cover the phenolic part of the substrate, forming three layers of planar rings. Our structure-based functional mutagenesis clarifies the roles of the residues involved in substrate binding and catalytic activity. Furthermore, distinct substrate-binding mechanisms between AsFaeE and other studied FAEs are identified. This investigation offers the initial structural insights into substrate recognition by SF6 FAEs, equipping us with structural knowledge that might facilitate the design of FAE variants capable of efficiently processing a wider range of substrate sizes.