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Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER + , MCF-7) and negative (ER - , MDA MB-231) cells within IC 50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER + and ER - cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -β., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cavoxin ( 1 ) was isolated as the main phytotoxin produced by Phoma cava Schulzer, a toxigenic fungus isolated from Castanea spp. Its structure was determined by 1D NMR and MS in 1985 along with that of the corresponding chroman-4-one cavoxone ( 2 ), an artifact formed by acid treatment of 1 . Since that time cavoxin was shown to be phytotoxic, antifungal, antifeedant, herbicidal, and antirust with potential application in agriculture and medicine. During a study aimed at improving cavoxin's production by P. cava , single crystals for X-ray diffractometric analysis were obtained. The X-ray crystallography characterization confirmed only in part the structure proposed for cavoxin ( 1 ), revealing a different substitution pattern on the aromatic ring, as depicted in the revised structure 3 .

Enhancing the selectivity of alpha 2 -adrenoceptor (α 2A -AR) agonists remains an unresolved issue. Herein, we reported the design of an α 2A -AR agonist using the conformation constraint method, beginning with medetomidine. The structure-activity relationship indicated that the 8-substituent of chromane derivatives exerted the most pronounced effect on α 2A -AR agonistic activity. Compounds A9 and B9 were identified as the most promising, exhibiting EC 50 values of 0.78 and 0.23 nM, respectively. Their selectivity indexes surpassed dexmedetomidine (DMED) by 10-80 fold. In vivo studies demonstrated that both A9 and B9 dose-dependently increased the loss of righting reflex in mice, with ED 50 values of 1.54 and 0.138 mg/kg, respectively. Binding mode calculations and mutation studies suggested the indispensability of the hydrogen bond between ASP128 3.32 and α 2A -AR agonist. In particular, A9 and B9 showed no dual reverse pharmacological effect, a characteristic exhibited by DMED in α 2A -AR activation.

A library of new chroman-4-one based 1,2,3-triazole analogues were synthesized involving a series of condensation, cyclization, Suzuki coupling and copper catalysed click chemistry protocols. The newly synthesized compounds 8a-l were screened for their invitro antioxidant and anti-inflammatory activities by employing Ascorbic acid and Diclofenac as reference drugs respectively. The compound without any substituent on benzyl ring (8a), compound with -Cl substituent in para position of benzyl ring (8i), and compound with ethoxy substituent in para position of benzyl ring (8k) exhibited potent antioxidant and anti-inflammatory activities with higher percentage of inhibition. To understand their binding affinities, molecular docking study of these three compounds performed against NADPH oxidase with presented outstanding docking scores and promising binding interactions like H-bond and hydrophobic., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This work presents a hydrothermal method followed by a sonochemical treatment for synthesizing tantalum decorated on iron selenide (Ta/FeSe 2 ) integrated with nitrogen-doped graphene (NGR) as a susceptible electrode material for detecting trolox (TRX) in berries samples. The surface morphology, structural characterizations, and electrochemical performances of the synthesized Ta/FeSe 2 /NGR composite were analyzed via spectrophotometric and voltammetry techniques. The GCE modified with Ta/FeSe 2 /NGR demonstrated an impressive linear range of 0.1 to 580.3 μM for TRX detection. Additionally, it achieved a remarkable limit of detection (LOD) of 0.059 μM, and it shows a high sensitivity of 2.266 μA μМ -1  cm -2 . Here, we used density functional theory (DFT) to investigate the structures of TRX and TRX quinone and the locations of energy levels and electron transfer sites. The developed sensor exhibits significant selectivity, satisfactory cyclic and storage stability, and notable reproducibility. Moreover, the practicality of TRX was assessed in different types of berries, yielding satisfactory recoveries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Programmed death-ligand 1 (PD-L1) has emerged as a promising therapeutic target for various cancers due to its crucial role in promoting tumor immune evasion. Here, we report a novel class of chroman-like small-molecule PD-L1 inhibitors exhibiting significant activity in inhibiting the PD-1/PD-L1 interaction. Employing a "ring-close" strategy for conformational restriction, we have achieved compound C27 , which demonstrates superior PD-1/PD-L1 inhibitory activity compared to the positive control. Molecular dynamics simulation and binding free energy calculation predict that ( R )-C27 with inhibitory activity surpassed ( S )-C27 . The experimental results from bioassay and X-ray structural analysis corroborate these findings. All these results collectively indicate that ( R )-C27 is a promising lead compound deserving further exploration.

A new method for the stereoselective metal-, additive- and oxidant-free Friedel-Crafts-type halo-carbocyclization of N - and O -tethered arene-olefin substrates is reported, involving reaction with a suitable electrophilic halogenating reagent (NXS/DCDMH) in hexafluoroisopropanol. All halo (X = Br, I, Cl)-functionalized tetrahydroquinolines and chromans were obtained in excellent yields and with high levels of diastereocontrol (dr = >99 : 1), and these products were successfully transformed into synthetically useful compounds such as dihydroquinolines and partial or full azahelicene compounds.

Aim: Literature reports suggest spirochromanone derivatives exhibit anticancer activity. Methodology: The authors designed and synthesized 18 spirochromanone derivatives ( Csp 1-18 ). The compounds were characterized and evaluated for anticancer activity against human breast cancer (MCF-7) and murine melanoma (B16F10) cell lines. Results: The anticancer activity ranged from 4.34 to 29.31 μm. The most potent compounds, Csp 12 and Csp 18 , were less toxic against the human embryonic kidney (HEK-293) cell line and ∼ two/∼fourfold selective toward MCF-7 than B16F10 in comparison to the reference, BG-45 . Csp 12 caused 28.6% total apoptosis, leading to significant cytotoxicity, and arrested the G2 phase of the cell cycle in B16F10 cells. A molecular docking study of Csp 12 exhibited effective binding at the active site of the epidermal growth factor receptor kinase domain. Conclusion: This study highlights the importance of spirochromanones as anticancer agents.

Malaria is a prevalent and lethal disease. The fast emergence and spread of resistance to current therapies is a major concern and the development of a novel line of therapy that could overcome, the problem of drug resistance, is imperative. Screening of a set of compounds with drug/natural product-based sub-structural motifs led to the identification of spirocyclic chroman-4-one 1 with promising antimalarial activity against the chloroquine-resistant Dd2 and chloroquine-sensitive 3D7 strains of the parasite. Extensive structure-activity and structure-property relationship studies were conducted to identify the essential features necessary for its activity and properties., (Copyright © 2022. Published by Elsevier Ltd.)

A novel series of 14 spiropyrrolidines bearing thiochroman-4-one/chroman-4-one, and oxindole/acenaphthylene-1,2-dione moieties were synthesized and characterized by spectroscopic techniques, as well as by three X-ray diffraction studies, corroborating the stereochemistry. Quantum chemical calculations studies, using the DFT approach, were performed to rationalize the stereochemical outcome. These N -heterocycles were evaluated for their antibacterial and antifungal activities against some pathogenic organisms. Several compounds displayed moderate to excellent activity towards the screened microbe strains in the study compared to Amoxicillin (AMX), Ampicillin (AMP), and Amphotericin B. Furthermore, a structural activity relationship (SAR) was established considering the synthesized compounds. Pharmacokinetic studies reveal that these derivatives exhibit an acceptable predictive ADMET profile (Absorption, Distribution, Metabolism, Excretion and Toxicity) and good drug-likeness.

Organic extract of the brown seaweed Turbinaria conoides (Sargassaceae) was chromatographically fractionated to yield an undescribed furanyl-substituted isochromanyl metabolite, named as turbinochromanone, which was characterized as methyl 4-[(3S)-8-{[(3R)-4-ethyl-2,3-dihydrofuran-3-yl]methyl}-1-oxo-3,4-dihydro-1H-2-benzopyran-3-yl]butanoate. The isochromanyl derivative possessed comparable attenuation potential against 5-lipoxygenase (IC 50 3.70 μM) with standard 5-lipoxygenase inhibitor drug zileuton (IC 50 2.41 μM). Noticeably, the index of anti-inflammatory selectivity of turbinochromanone (∼1.7) was considerably greater than that exhibited by the standard agent diclofenac (1.06). Antioxidant properties of turbinochromanone against oxidants (IC 50 ∼24 μM) further supported its potential anti-inflammatory property. Greater electronic properties (topological polar surface area of 61.8) along with comparatively lesser docking parameters of the studied compound with aminoacyl residues of targeted enzymes (cyclooxygenase-2 and 5-lipoxygenase) (binding energy of -11.05 and -9.40 kcal mol -1 , respectively) recognized its prospective anti-inflammatory potential. In an aim to develop seaweed-based natural anti-inflammatory leads, the present study isolated turbinochromanone as promising 5-lipoxygenase and cyclooxygenase-2 inhibitor, which could be used for pharmaceutical and biotechnological applications., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Penicisteckins A-D ( 1 - 4 ), two pairs of atropodiastereomeric biaryl-type hetero- and homodimeric bis-isochromans with 7,5'- and 7,7'-linkages and a pair of atropodiastereomeric 2-(isochroman-5-yl)-1,4-benzoquinone derivatives [penicisteckins E ( 5 ) and F ( 6 )], were isolated from the Penicillium steckii HNNU-5B18. Their structures including the absolute configuration were determined by extensive spectroscopic and single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Both the bis-isochromans and the isochroman/1,4-benzoquinone conjugates represent novel biaryl scaffolds containing both central and axial chirality elements. The monomer anserinone B ( 8 ) exhibited potent antibacterial activities against Staphylococcus aureus ATCC 29213 and methicillin-resistant Staphylococcus aureus with minimal inhibition concentration values ranging from 2 to 8 μg mL -1 . Plausible biosynthetic pathways of 1 - 6 are proposed, which suggest how the absolute configurations of the isolates were established during the biosynthetic scheme.

In this study, the antioxidant and antiradical properties of some phyto lignans (nordihydroguaiaretic acid, secoisolariciresinol, secoisolariciresinol diglycoside, and α-(-)-conidendrin) and mammalian lignans (enterodiol and enterolactone) were examined by different antioxidant assays. For this purpose, radical scavenging activities of phyto and mammalian lignans were realized by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS •+ ) scavenging assay and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Additionally, the reducing ability of phyto and mammalian lignans were evaluated by cupric ions (Cu 2+ ) reducing (CUPRAC) ability, and ferric ions (Fe 3+ ) and [Fe 3+ -(TPTZ)2] 3+ complex reducing (FRAP) abilities. Also, half maximal inhibitory concentration (IC 50 ) values were determined and reported for DPPH • and ABTS •+ scavenging influences of all of the lignan molecules. The absorbances of the lignans were found in the range of 0.150-2.320 for Fe 3+ reducing, in the range of 0.040-2.090 for Cu 2+ reducing, and in the range of 0.360-1.810 for the FRAP assay. On the other hand, the IC 50 values of phyto and mammalian lignans were determined in the ranges of 6.601-932.167 µg/mL for DPPH • scavenging and 13.007-27.829 µg/mL for ABTS •+ scavenging. In all of the used bioanalytical methods, phyto lignans, as secondary metabolites in plants, demonstrated considerably higher antioxidant activity compared to that of mammalian lignans. In addition, it was observed that enterodiol and enterolactone exhibited relatively weaker antioxidant activities when compared to phyto lignans or standard antioxidants, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), Trolox, and α-tocopherol.

Interleukin-17 (IL-17) is a proinflammatory cytokine that plays a dominant role in inflammation, autoimmunity, and host defense. RORγt is a key transcription factor mediating T helper 17 (Th17) cell differentiation and IL-17 production, which is able to activate CD8 + T cells and elicit antitumor efficacy. A series of sulfonamide derivatives as novel RORγt inverse agonists were designed and synthesized. Using GSK2981278 (phase II) as a starting point, we engineered structural modifications that significantly improved the activity and pharmacokinetic profile. In animal studies, oral administration of compound d3 showed a robust and dose-dependent inhibition of the IL-17A cytokine expression in a mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that the compound d3 occupied the active pocket suitably. Thus, compound d3 was selected as a clinical compound for the treatment of Th17-driven autoimmune diseases.

2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3-chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee., (© 2021 Wiley-VCH GmbH.)

Phytochemical investigation of the ethanol extract of underground parts of Iris tenuifolia Pall. afforded five new compounds; an unusual macrolide termed moniristenulide ( 1 ), 5-methoxy-6,7-methylenedioxy-4- O -2'-cycloflavan ( 2 ), 5,7,2',3'-tetrahydroxyflavanone ( 3 ), 5-hydroxy-6,7-dimethoxyisoflavone-2'- O - β -d-glucopyranoside ( 9 ), 5,2',3'-dihydroxy-6,7-dimethoxyisoflavone ( 10 ), along with seven known compounds ( 4 - 8 , 11 - 12 ). The structures of all purified compounds were established by analysis of 1D and 2D NMR spectroscopy and HR-ESI-MS. The antimicrobial activity of the compounds 1 - 3 , 5 , 9 , and 10 was investigated using the agar diffusion method against fungi, Gram-positive and Gram-negative bacteria. In consequence, new compound 3 was found to possess the highest antibacterial activity against Enterococcus faecalis VRE and Mycobacterium vaccae . Cell proliferation and cytotoxicity tests were also applied on all isolated compounds and plant crude extract in vitro with the result of potent inhibitory effect against leukemia cells. In particular, the newly discovered isoflavone 10 was active against both of the leukemia cells K-562 and THP-1 while 4 - 6 of the flavanone type compounds were active against only THP-1.

The precise understanding of the behaviour of vitamin E (α-tocopherol; Toc) complexed with cyclodextrin (CD) additives in aqueous solution is a fundamental issue for further development of their aqua-related biological applications. In this study, the solubilisation and complexation behaviours of Toc with methyl-substituted CD derivatives and the radical scavenging ability of the resulting complexes were precisely investigated in water media. Several problems were encountered upon pre-dissolving Toc in an organic solvent prior to the addition to the water media, such as enhancement of the dispersibility and decrease in the complexation capacity. Additionally, dispersions were obtained in some cases when mixing CD and Toc even in the absence of an organic solvent; therefore, to perform the measurements, a transparent solution was prepared via filtration with a nanopore filter. Consequently, unexpectedly, the addition of certain CD methylated derivatives did not always enhance the solubility of Toc significantly. However, 2,6-di-O-methylated β-CD (2,6-DMCD) formed a water-soluble inclusion complex with Toc, effectively enhancing its solubility. A phase solubility study indicated the formation of 1:2 or 1:3 Toc/CD inclusion complexes, and the interaction of 2,6-DMCD with both the chromanol head and the phytol chain of Toc was revealed by 2D ROESY nuclear magnetic resonance analysis. The interaction between 2,6-DMCD and the chromanol head was also confirmed for a 2,6-DMCD-2,2,5,7,8-pentamethyl-6-chromanol inclusion complex. Additionally, a rapid scavenging effect for molecularly dissolved Toc was demonstrated even in a system comprising a chromanol head directly encapsulated by CD. Hence, this work elucidated the precise complexation and radical scavenging ability of 2,6-DMCD-Toc in an aqueous solution, which paves the way for its biological applications.

Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1 - 17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.

In this study, using the botanical active component thiochromanone as the lead compound, a total of 32 new thiochromanone derivatives containing a carboxamide moiety were designed and synthesized and their in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae ( Xoo ), Xanthomonas oryzae pv. oryzicolaby ( Xoc ), and Xanthomonas axonopodis pv. citri ( Xac ) were determined, as well as their in vitro antifungal activities against Botryosphaeria dothidea ( B. dothidea ), Phomopsis sp., and Botrytis cinerea ( B. cinerea ). Bioassay results demonstrated that some of the target compounds exhibited moderate to good in vitro antibacterial and antifungal activities. In particular, compound 4e revealed excellent in vitro antibacterial activity against Xoo , Xoc , and Xac , and its EC 50 values of 15, 19, and 23 μg/mL, respectively, were superior to those of Bismerthiazol and Thiodiazole copper. Meanwhile, compound 3b revealed moderate in vitro antifungal activity against B. dothidea at 50 μg/mL, and the inhibition rate reached 88%, which was even better than that of Pyrimethanil, however, lower than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing a carboxamide moiety.

A series of multitarget-directed ligands (MTDLs) was designed by functionalizing a pseudo-irreversible butyrylcholinesterase (BChE) inhibitor. The obtained hybrids were investigated in vitro regarding their h BChE and h AChE inhibition, their enzyme kinetics, and their antioxidant physicochemical properties (DPPH, ORAC, metal chelating). In addition, in vitro assays were applied to investigate antioxidant effects using murine hippocampal HT22 cells and immunomodulatory effects on the murine microglial N9 cell line. The MTDLs retained their antioxidative properties compared to the parent antioxidant-moieties in vitro and the inhibition of h BChE was maintained in the submicromolar range. Representative compounds were tested in a pharmacological Alzheimer's disease (AD) mouse model and demonstrated very high efficacy at doses as low as 0.1 mg/kg. The most promising compound was also tested in BChE -/- mice and showed reduced efficacy. In vivo neuroprotection by BChE inhibition can be effectively enhanced by incorporation of structurally diverse antioxidant moieties.

A series of thirty-one novel 7-(5-((amino)-methyl)-thiophen-2-yl)-spiro-[chroman-2,4'-piperidin]-4-one hydrochloride analogues (Cst 1 - 31) have been designed, synthesized and characterized by 1 H NMR, 13 C NMR and MS spectral analysis. Here, we evaluated the anticancer potential and biological results of low-molecular-weight bridgehead oxygen and nitrogen-containing spirochromanones on proliferation and apoptosis of the human breast cancer cell line (MCF-7) and Murine melanoma (B16F10). The anticancer activity ranged from 2.9 to 35.0 µM. The most potent compounds Cst-22, Cst-24 and Cst-31 were found to be less toxic against human embryonic kidney (HEK-293) cell lines. Cst-24 and Cst-31 were found to be causing significant cytotoxicity through apoptotic cell death and also G2 phase arrest of cell cycle in B16F10 cells. In-silico ADME prediction stidies of the titled compounds were found within the rules outlined, and these compounds may not face any pharmacokinetic associated issues in the mere future upon developmental stage. These conjugates may serve as a lead for the discovery of potential anticancer drug candidate with better therapeutic profile., (Copyright © 2021 Elsevier Inc. All rights reserved.)

An efficient and mild synthetic approach for 2-alkyl-substituted chroman-4-ones via zinc-mediated cascade decarboxylative β-alkylation and dechlorination of 3-chlorochromones was developed. This transformation employed commercially available starting materials and was performed under mild conditions without heat, visible light, peroxide or heavy metals. Moreover, various alkyl NHPI esters with functional groups and differently substituted 3-chlorochromones were tolerated, affording the targeted products with moderate to excellent yields. This protocol could be utilized to construct a diverse library of 2-substituted chroman-4-one derivatives, which could be useful in the discovery of lead compounds for drug discovery in the future.

Antioxidant interactions of γ-terpinene with α-tocopherol mimic 2,2,5,7,8-pentamethyl-6-chromanol (PMHC) and caffeic acid phenethyl ester (CAPE), used as models, respectively, of mono- and poly-phenols were demonstrated by differential oximetry during the inhibited autoxidation of model substrates: stripped sunflower oil, squalene, and styrene. With all substrates, γ-terpinene acts synergistically regenerating the chain-breaking antioxidants PMHC and CAPE from their radicals, via the formation of hydroperoxyl radicals. The inhibition duration for mixtures PMHC/γ-terpinene and CAPE/γ-terpinene increased with γ-terpinene concentration, while rate constants for radical-trapping were unchanged by γ-terpinene, being 3.1 × 10 6 and 4.8 × 10 5  M -1 s -1 for PMHC and CAPE in chlorobenzene (30 °C). Using 3,5-di-tert-butylcatechol and 3,5-di-tert-butyl-1,2-bezoquinone we demonstrate that γ-terpinene can reduce quinones to catechols enabling their antioxidant activity. The different synergy mechanism of γ-terpinene with mono- and poly-phenolic antioxidants is discussed and its relevance is proven in homogenous lipids using natural α-tocopherol and hydroxytyrosol as antioxidants, calling for further studies in heterogenous food products., (Copyright © 2020. Published by Elsevier Ltd.)

Essential oils (EOs) were extracted from Eugenia patrisii , E. punicifolia , and Myrcia tomentosa, specimens A and B, using hydrodistillation. Gas chromatography coupled with mass spectrometry (GC/MS) was used to identify the volatile constituents present, and the antioxidant capacity of EOs was determined using diphenylpicryl-hydrazyl (DPPH) and trolox equivalent antioxidant capacity (TEAC) assays. For E. patrisii , germacrene D (20.03%), bicyclogermacrene (11.82%), and ( E )-caryophyllene (11.04%) were identified as the major constituents of the EOs extracted from specimen A, whereas specimen B primarily comprised γ-elemene (25.89%), germacrene B (8.11%), and ( E )-caryophyllene (10.76%). The EOs of E. punicifolia specimen A contained β-Elemene (25.12%), ( E )-caryophyllene (13.11%), and bicyclogermacrene (9.88%), while specimen B was composed of ( E )-caryophyllene (11.47%), bicyclogermacrene (5.86%), β-pinene (5.86%), and γ-muurolene (5.55%). The specimen A of M . tomentosa was characterized by γ-elemene (12.52%), germacrene D (11.45%), and ( E )-caryophyllene (10.22%), while specimen B contained spathulenol (40.70%), α-zingiberene (9.58%), and γ-elemene (6.89%). Additionally, the chemical composition of the EOs was qualitatively and quantitatively affected by the collection period. Furthermore, the EOs of the studied specimens, especially specimen A of E. punicifolia , showed a greater antioxidant activity in DPPH rather than TEAC, as represented by a significantly high inhibition percentage (408.0%).

As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound B16 inhibited the proliferation of enzalutamide-resistant 22Rv1 cells with an IC 50 value of 96 nM. Furthermore, compounds B16 - P2 displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model.

A series of novel thiochromanone derivatives containing a sulfonyl hydrazone moiety were designed and synthesized. Their structures were determined by 1 H-NMR, 13 C-NMR, and HRMS. Bioassay results showed that most of the target compounds revealed moderate to good antibacterial activities against Xanthomonas oryzae pv. oryzae , Xanthomonas oryzae pv. oryzicolaby , and Xanthomonas axonopodis pv. citri . Compound 4i had the best inhibitory activity against Xanthomonas oryzae pv. oryzae , Xanthomonas oryzae pv. oryzicolaby , and Xanthomonas axonopodis pv. citri , with the EC 50 values of 8.67, 12.65, and 10.62 μg/mL, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, bioassay results showed that all of the target compounds proved to have lower antifungal activities against Sclerotinia sclerotiorum , Fusarium oxysporum , Gibberella zeae , Rhizoctonia solani , Verticillium dahlia , and Botrytis cinerea than those of Carbendazim.

Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD calculation. The Δ 10,11 double bond of pestaloficin D (5) was revised to E-configurated based on the extensive spectroscopic analyses. Compounds 1a/1b and 2a/2b were the first examples of enantiomeric isoprenylated chromane derivatives, which were successfully separated by chiral HPLC. Additionally, all the isolated compounds were evaluated for the in vitro β-glucuronidase (GUS) and butyrylcholinesterase (BChE) inhibitory activities. Compounds 1a and 1b showed significant β-glucuronidase inhibitory potency with IC 50 values of 7.6 and 10.3 μM, respectively. Compound 14 exhibited moderate BChE inhibitory activity with an IC 50 value of 21.3 μM. In addition, the structure-enzyme inhibitory activity relationship of compounds 1-14 is discussed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O 2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

Singlet oxygen ( 1 O 2 ) is the major reactive oxygen species ROS causing photooxidative stress in plants which is formed predominantly in the reaction center of photosystem II during photosynthesis. To avoid deleterious effects of 1 O 2 oxygen on photosynthetic membrane components, plant synthesize a variety of 1 O 2 quenchers of lipophilic character, such as carotenoids or phenolic prenyllipids (tocopherols, plastochromanol-8, plastoquinol). In the process of chemical quenching of 1 O 2 by the antioxidants, both short-lived products, such as oxidized carotenoids, or relative long-lived compounds, such as oxidized phenolic prenyllipids are formed. The other target of 1 O 2 are unsaturated fatty acids of membrane lipids that undergo peroxidation as a result of the reaction. Some of the 1 O 2 oxidation products, like β-cyclocitral can be components of 1 O 2 -signallingsignaling pathway leading to acclimatory responses of plants, while some others further fulfill antioxidant functions, like hydroxy-plastochromanol or hydroxy-plastoquinol. As most of the 1 O 2 oxidation products are specific compounds formed only as a results of 1 O 2 action, they can be very useful, specific molecular markers of 1 O 2 -dependent oxidative stress in vivo., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The development of practical C-H/C-H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C-C bonds. Herein we report a cyclative C(sp 3 )-H/C(sp 2 )-H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-N-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na 2 CO 3 ·1.5H 2 O 2 ) as the sole oxidant and generates water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, can be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through sequential functionalizations of four C-H bonds.

Isochromans are well recognized heterocyclic compounds in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Medicinal chemistry investigators have synthesized drug-like isochroman candidates with multiple medicinal features including central nervous system (CNS), antioxidant, antimicrobial, antihypertensive, antitumor and anti-inflammatory agents. Simultaneously, SAR (Structure-Activity Relationship) analysis has drawn attentions among medicinal chemists, along with a great deal of derivatives have been derived for potential targets. In this article, we thoroughly summarize the biological activities and part of typical SAR for isochroman derivatives reported on existing literatures and patents, wishing to provide an overall retrospect and prospect on the isochroman analogues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Masson SAS.)

The spiro[chromane-2,4'-piperidine]-4(3H)-one is an important pharmacophore. It is a structural component in many drugs, drug candidates (or lead compounds) and various biochemical reagents. This review demonstrated an impressive progress in syntheses of spiro[chromane-2,4'-piperidine]-4(3H)-one-derived compoundsin the recent years and focuses on features of their biological relevance's. The prospects for the development of new biologically active substances containing a spiro[chromane-2,4'-piperidine]-4(3H)-one pharmacophore are analyzed and briefly discussed in terms of its structure, reaction, mechanism, scope and potential utility., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Terpenes, wide-spread secondary plant metabolites, constitute important parts of many natural compounds that hold various biological activities, including antioxidant, calming, antiviral, and analgesic activities. Due to their high volatility and low solubility in water, studies of compounds based on terpenes are difficult, and methodologies must be adjusted to their specific characteristics. Considering the significant influence of iron ions on dementia development, the activity of terpenes in reducing Fe 3+ represents an important area to be determined. Previously obtained results were unreliable because ferric-reducing antioxidant power (FRAP) methodology was not adjusted regarding studying terpenes. Taking this fact into account, the aim of this study was to optimize the method for monoterpene assessment. The study included three modifications, namely, (1) slightly adjusting the entire FRAP procedure, (2) replacing methanol with other solvents (heptane, butanone, or ethyl acetate), and (3) adding Tween 20. Additionally, a thin layer chromatography (TLC) -FRAP assay was performed. The obtained results revealed significant improvement in the reduction activity of selected terpenes (linalool, α-phellandrene, and α-terpinene) in studies with Tween 20, whereas replacing methanol with other solvents did not show the expected effects.

Receptor activator of nuclear factor-κB ligand (RANKL) constitutes the master mediator of osteoclastogenesis, while its pharmaceutical inhibition by a monoclonal antibody has been approved for the treatment of postmenopausal osteoporosis. To date, the pursuit of pharmacologically more favorable approaches using low-molecular-weight inhibitors has been hampered by low specificity and high toxicity issues. This study aimed to discover small-molecule inhibitors targeting RANKL trimer formation. Through a systematic screening of 39 analogues of SPD-304, a dual inhibitor of tumor necrosis factor (TNF) and RANKL trimerization, we identified four compounds ( 1b , 3b , 4a , and 4c ) that selectively inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, without affecting TNF activity or osteoblast differentiation. Based on structure-activity observations extracted from the most potent and less toxic inhibitors of RANKL-induced osteoclastogenesis, we synthesized a focused set of compounds that revealed three potent inhibitors ( 19a , 19b, and 20a ) with remarkably low cell-toxicity and improved therapeutic indexes as shown by the LC 50 to IC 50 ratio. These RANKL-selective inhibitors are an excellent starting point for the development of small-molecule therapeutics against osteolytic diseases.

Background: The aim of the present work was to set-up compounds that are able to act simultaneously as antimalarial and antioxidants. Trolox, a known antioxidant was chosen as a core structure to ensure the antioxidant activity and contribute to antiplasmodial effect. Results: Ten compounds were prepared in one step and evaluated on chloroquino-sensitive (3D7) and chloroquino-resistant (FcB1) strains of Plasmodium falciparum . The most active compound ( 3d ) shows antiplasmodial activity in the range of chloroquine against chloroquino-sensitive and chloroquino-resistant P. falciparum strain. The antioxidant activity of ( 3d ) was conducted through four tests and was found to be more potent than trolox itself and L-ascorbic acid. Conclusion: Compound ( 3d ) can be considered as an excellent lead molecule for further in vivo studies. This study paves the way for building large chemical libraries to be investigated in the field of malaria.

Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb "Manshanfong" used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum , is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC 50 of 4 µM. The structure-activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid β aggregation. These results may help in the design of effective drugs based on DCA.

Tumor necrosis factor α (TNF-α) is an important therapeutic target for rheumatoid arthritis, inflammatory bowel disease, and septic hepatitis. In this study, structure-based virtual ligand screening combined with in vitro and in vivo assays were applied. A lead compound, benpyrine, could directly bind to TNF-α and block TNF-α-trigged signaling activation. Furthermore, the endotoxemic murine model showed that benpyrine could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury. Meanwhile, administration of benpyrine by gavage significantly relieved the symptoms of collagen-induced arthritis and imiquimod-induced psoriasiform inflammation in mice. Thus, our study discovered a novel, highly specific, and orally active small-molecule TNF-α inhibitor that is potentially useful for treating TNF-α-mediated inflammatory and autoimmune disease.

Acetyl-CoA carboxylases (ACCs) are the rate-limiting enzymes in the de no lipogenesis, which play an important role in the synthesis and oxidation of fatty acid. Recent research reveals that ACCs are tightly relevant to many kinds of metabolic diseases and cancers. In this study, we synthesized a series of chroman derivatives and evaluated their ACCs inhibitory activities, obtaining compound 4s with IC 50 value of 98.06 nM and 29.43 nM of binding activities in ACC1 and ACC2, respectively. Compound 4s exhibited the most potent anti-proliferation activity against A549, H1975, HCT116 and H7901 cell lines (values of IC 50 : 0.578 μΜ, 1.005 μΜ, 0.680 μΜ and 1.406 μΜ, respectively). Docking studies were performed to explain the structure-activity relationships. These results indicate that compound 4s is a promising ACC1/2 inhibitor for the potent treatment of cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Curcumin is claimed to have many health benefits, but it has low chemical stability. In this study, the influence of food-grade antioxidants on the chemical degradation of curcumin-enriched oil-in-water emulsions was examined. The curcumin degradation rate and extent depended on antioxidant type. The water-soluble antioxidants were more effective at protecting curcumin from degradation than the oil-soluble ones, which may have been because curcumin degrades faster in water than in oil. Interestingly, the amphiphilic antioxidant was almost as effective as the water-soluble ones. The oil-soluble antioxidant actually slightly promoted curcumin degradation. In summary, curcumin retention after storage declined in the following order: 82.6% (Trolox) ~82.2% (ascorbic acid) >79.5% (ascorbyl palmitate) ≫57.9% (control) >52.7% (α-tocopherol). The effectiveness of ascorbic acid in stabilizing curcumin increased as its concentration was raised (0-300 μM). Our results may facilitate the creation of curcumin-enriched foods and beverages with enhanced bioactivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A series of ten chalcones (7a-j) and five new dihydrochromane-chalcone hybrids (7k-o) were synthesized and identified using spectroscopic techniques (IR, NMR, and MS). All compounds were evaluated in vitro against the B. cinerea and M. fructicola phytopathogens that affect a wide range of crops of commercial interest. All compounds were tested against both phytopathogens using the mycelial growth inhibition test, and it was found that two and five compounds had similar activity to that of the positive control for B. cinerea (7a = 43.9, 7c = 45.5, and Captan ® = 24.8 µg/mL) and M. fructicola (7a = 48.5, 7d = 78.2, 7e = 56.1, 7f = 51.8, 7n = 63.2, and Mystic ® = 21.6 µg/mL), respectively. To understand the key chalcone structural features for the antifungal activity on B. cinerea and M. fructicola, we developed structure-activity models with good statistical values (r 2 and q 2 higher than 0.8). For B. cinerea, the hydrogen bonding donor and acceptor and the atomic charge on C 5 modulate the mycelial growth inhibition activity. In contrast, dipole moment and atomic charge on C 1' and the carbonyl carbon modify the inhibition activity for M. fructicola. These results allow the design of other compounds with activities superior to those of the compounds obtained in this study.

The present study examines a series of six biologically-active flavonoid and chromanone derivatives by X-ray crystal structure analysis: (E)-3-benzylidene-2-phenylchroman-4-one, C 22 H 16 O 2 , I, (E)-3-(4-methylbenzylidene)-2-phenylchroman-4-one, C 23 H 18 O 2 , II, (E)-3-(3-methylbenzylidene)-2-phenylchroman-4-one, C 23 H 18 O 2 , III, (E)-3-(4-methoxybenzylidene)-2-phenylchroman-4-one, C 23 H 18 O 3 , IV, (E)-3-benzylidenechroman-4-one, C 16 H 12 O 2 , V, and (E)-3-(4-methoxybenzylidene)chroman-4-one, C 17 H 14 O 3 , VI. The cytotoxic activities of the presented crystal structures have been determined, together with their intermolecular interaction preferences and Hirshfeld surface characteristics. An inverse relationship was found between the contribution of C...C close contacts to the Hirshfeld surface and cytotoxic activity against the WM-115 cancer line. Dependence was also observed between the logP value and the percentage contribution of C...H contacts to the Hirshfeld surface.

Sesamol is a phenolic derivative. Its antioxidant activity is low than that of Trolox and depends on benzodioxole moiety. Thus, a molecular modification strategy through alkylation, inspired by natural and synthetic antioxidants, was studied by molecular modeling at the DFT/B3LYP level of theory by comparing the 6-31+G(d,p) and 6-311++G(2d,2p) basis sets. All proposed derivatives were compared to classical related antioxidants such as Trolox, t -butylated hydroxytoluene (BHT) and t -butylated hydroxyanisole (BHA). According to our results, molecular orbitals, single electron or hydrogen-atom transfers, spin density distributions, and alkyl substitutions at the ortho positions related to phenol moiety were found to be more effective than any other positions. The trimethylated derivative was more potent than Trolox. t -Butylated derivatives were stronger than all other alkylated derivatives and may be new alternative forms of modified antioxidants from natural products with applications in the chemical, pharmaceutical, and food industries.

Menthyl anthranilate (MA, tradename meradimate) is a UV-A absorber. The interactions of ground-state molecular oxygen with the long-lived triplet state of MA produce singlet oxygen through energy transfer. The quantum yield of singlet oxygen generation is 0.12 in air-saturated ethanol. Kinetic traces of the near-IR phosphorescence of singlet oxygen generated by MA-photosensitization have been measured in the absence and presence of Trolox (a water-soluble analogue of vitamin E and a quencher of singlet oxygen) and α-tocopherol (vitamin E, a natural antioxidant) in ethanol. Fluorescence and transient absorption measurements suggest that Trolox and α-tocopherol quench the lowest excited singlet and triplet states of MA. As a result, Trolox and α-tocopherol suppress MA-photosensitized singlet oxygen generation. Not only the quenching of singlet oxygen but also the suppression of singlet oxygen generation is the mechanism of antioxidant properties of Trolox and α-tocopherol for MA. The ability of α-tocopherol to suppress the MA-photosensitized singlet oxygen generation in isododecane, used as a solvent for an oil-soluble UV absorber, is close to that in ethanol. Suppression of sunscreen-photosensitized singlet oxygen generation is an important method for the formulation of safe cosmetic sunscreens.

Voltage-gated sodium channel Na V 1.7 is a genetically validated target for pain. Identification of Na V 1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent Na V 1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over Na V 1.5, and CYP2C9 inhibition. The lead molecules 13 , 29 , 32 , 43 , and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.

Because of their biocompatibility and biosafety, pegylated Au NPs (Au@PEG), as a nanodrug-carrier, have been widely applied in different biomedical applications, including imaging and drug delivery systems. Under such conditions, the biosafety of Au@PEG has attracted tremendous attention. However, only a small number of studies focused on the neurotoxicity of Au@PEG used as drug delivery carriers not to mention reducing the neurotoxicity of Au@PEG. To address this issue, the adverse effects of Au@PEG on human neuroblastoma SHSY5Y cells were first investigated. The results showed that 4.5 nm Au@PEG significantly induced cell apoptosis through upregulating reactive oxygen species (ROS) production and disordering the mitochondrial membrane potential. To further evaluate whether the neurotoxicity of Au@PEG could be improved through conjugating antioxidants on the surface of Au@PEG, Trolox (a vitamin E analogue)-functionalized Au@PEG (Au@Trolox) was synthesized. The results showed that the neurotoxicity of Au@PEG on SHSY5Y cells could be significantly improved by Au@Trolox. Next, mice were subjected to administration of 4.5 nm Au@PEG and Au@Trolox for 3 months. An increase of oxidative stress and a decrease in the activity of key antioxidant enzymes including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were observed after long-term injection of Au@PEG. More importantly, both the apoptosis of neurons and the activation of astrocytes were observed in the hippocampus of mice injected with Au@PEG. In contrast, the adverse effects of Au@PEG could be improved when injected with Au@Trolox. In short, the present study provided new insights into the toxicity evaluation of nanoparticles and would help to better understand and prevent the neurotoxicity of nanomaterials used in pharmaceutics.

Moracin T is a natural product isolated from Morus mesozygia (Moraceae), which acts as potent antioxidant agent. In this study, density functional theory-based computational methods have been performed to evaluate systematically the radical scavenging behaviour of this compound. Structural characteristics such as frontier molecular orbitals and molecular electrostatic potential mapping have been investigated. Thermodynamic parameters related to the three main antiradical mechanisms, hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT), and sequential proton loss electron transfer (SPLET) have been studied. In addition, two variants of SPLET mechanism namely sequential proton loss hydrogen atom transfer (SPLHAT) and double sequential proton loss electron transfer (D-SPLET) have been investigated. The reaction of moracin T with hydroperoxyl radical (HOO • ), as representative reactive oxygen species, was also studied. The obtained results are of great significance in better understanding the chemical mechanism of the radical-scavenging action and open new perspectives for the design of new potent antioxidant agents.

Tocosol™ is a tocopherol-based paclitaxel (PTX) nanoemulsion consisting of α-tocopherol (α-T) isomer of vitamin E as a solubilizer and vitamin E TPGS as the primary emulsifier. Despite its positive attributes in early clinical studies, it failed the pivotal phase III clinical trials. The long-term goal of this work was to reformulate Tocosol™. In this study, Tocosol™ formulation was optimized by replacing the α-T isomer with the more pharmacological active isomer γ-tocotrienol (γ-T 3 ), and the surfactant vitamin E TPGS was replaced with in-house designed PEGylated γ-T 3 surfactant. The reformulated paclitaxel γ-T 3 /PEGylated γ-T 3 -based nanoemulsion was significantly more active against pancreatic tumor cell lines than α-T/Vitamin E TPGS based formulation (IC 50 = 0.5 μM and 1.1 μM, respectively). Furthermore, the reformulated product showed an average size of 220 ± 6 nm with surface charge equal to -42 ± 2 mV. The optimized product was physically and chemically stable over 6 months per ICH storage condition guidelines.

Peptides from enzymatic hydrolysates of food proteins exhibit significant antioxidant activity. Several studies have attempted to determine the factors contributing to the antioxidant activity of peptides; however, the physicochemical properties and factors essential for the antioxidant activity of peptides are still unclear. In this study, in order to clarify the factors important for peptide antioxidant activity based on the properties of component amino acids, 55 tripeptides were synthesized from 20 natural amino acids and their antioxidant activity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay system. The tripeptides were divided into two data sets: a training set comprising 50 compounds and a validated set comprising five compounds. The structure-activity relationship of the training set was then analyzed using classical quantitative structure-activity relationship (QSAR) analysis. The study findings demonstrate that the presence of a cysteine residue at any position, an aromatic amino acid at the C-terminus, higher hydrophobicity of the N-terminal residue, and smaller HOMO-LUMO energy gap of the middle residue can significantly enhance the antioxidant activity. The activities of the five validated compounds were predicted using the constructed QSAR model, and a good correlation between measured and predicted activities was observed. The information obtained from the QSAR model could be useful for effective production of antioxidant peptides from food proteins such as egg white proteins., (© 2020 European Peptide Society and John Wiley & Sons, Ltd.)

Chromane, which has a fused cyclic structure, is a significant molecule that can be found in the structure of many important compounds. Lactobacillus paracasei BD101 was demonstrated as whole-cell biocatalyst for the synthesis of (S)-6-chlorochroman-4-ol with immense enantioselectivity. The conditions of asymmetric reduction were optimized one factor by one factor using L paracasei BD101 to achieve enantiomerically pure product and complete conversion. Using these obtained optimization conditions, asymmetric reduction of 6-chlorochroman-4-one was performed under environmentally friendly conditions; 6-chlorochroman-4-one, having a fused cyclic structure as previously noted to be difficult to asymmetric reduction with biocatalysts, was enantiomerically reduced to (S)-6-chlorochroman-4-ol with an enantiomeric excess >99% on a high gram scale. This study is the first example in the literature for the enantiopure synthesis of (S)-6-chlorochroman-4-ol using a biocatalyst. Also notably, the optical purity of (S)-6-chlorochroman-4-ol obtained in this study through asymmetric bioreduction using whole-cell biocatalyst is the highest value in the literature. In this study, (S)-6-chlorochroman-4-ol was produced on a gram scale by an easy, inexpensive, and environmentally friendly method, which has shown the production of valuable chiral precursors for drug synthesis and other industrial applications. This study provides a convenient method for the production of (S)-6-chlorochroman-4-ol, which can meet the industrial green production demand of this chiral secondary alcohol., (© 2020 Wiley Periodicals, Inc.)

Carboxymethyl cellulose (CMC)-based films were developed by incorporating green coffee oil (GCO) obtained by cold pressing and hydroalcoholic extracts of its residues. The effect of cake (CE) and sediment extracts (SE) in different proportions (20-40%) and GCO on chemical, morphological, physical, mechanical, optical, and antioxidant properties of the films was investigated. Eight fatty acids and four major phenolic compounds were identified by High-Resolution Direct-Infusion Mass Spectrometry in GCO and residue extracts. FTIR indicated interactions among CMC, phenolic compounds, and fatty acids. Films enriched with residue extracts presented heterogeneous microstructure. The tensile strength of the films decreased from 58 to 3 MPa with the extracts concentration, while elongation increased from 28 to 156% (p < 0.05). The water vapor permeability (averaging 3.94 × 10 -8  g mm/cm 2  h Pa) was not significantly affected by the extracts and GCO. The surface color was influenced by the type and concentration of extracts (p < 0.05), the film with SE40% had remarkable UV-vis barrier properties. The incorporation of GCO residue extracts imparted high antioxidant capacity to the CMC-based films, especially with CE40% (643.8 µmol Trolox eq./g dried film; 51.3 mg GAE/g dried film). General observations indicated the potential of these films, mainly the ones containing CE, like active packaging material for food applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)