Isolation and Quantification of Palmatine from Fibraurea tinctoria Lour: In Vitro Antioxidant Activity and In Silico Antidiabetic Activity Evaluation.

Purpose: This study aimed to isolate and characterize palmatine from Fibraurea tinctoria Lour stems, quantify its content, and determine its antioxidant and antidiabetic activities. Patients and Methods: Palmatine was isolated from the methanol extract of Fibraurea tinctoria Lour stems by silica gel column chromatography. Structural elucidation of the isolated compounds was performed using spectral data analysis and comparison with the literature. High-Performance Liquid Chromatography (HPLC) was used to quantitatively determine palmatine in the crude methanol extract and fractions. The DPPH and non-enzymatic SOD mimic methods were used to assess the antioxidant activity of the methanol extract, fractions, and isolated compounds. The antidiabetic activity was evaluated in silico by the molecular docking method of alpha-glucosidase and DPP-IV enzymes. Palmatine was used as a test ligand and was compared with berberine and its native ligand or standard compounds. Results: The isolated compound was identified as palmatine. Quantification of palmatine compound by HPLC showed that palmatine was found in the extract and all fractions. In the in vitro antioxidant activity test using the DPPH method, fraction 4 showed the highest activity, with an IC50 value of 91 ppm. In contrast, using the non-enzymatic SOD mimic method, the methanol extract, fraction 5, and isolated compound (palmatine) exhibited very strong antioxidant activity, with IC50 values of 18, 20, and 28 ppm, respectively. The in silico antidiabetic activity of palmatine is thought to have the potential to inhibit these two enzymes. Conclusion: These results showed that Fibraurea tinctoria Lour stems have potential as an antioxidant and antidiabetic agent. Further research on phytochemical and pharmacological is required to validate the use of this plant species for the treatment of various diseases, especially diabetes mellitus.

Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear.

Treatment-induced ototoxicity and accompanying hearing loss are a great concern associated with chemotherapeutic or antibiotic drug regimens. Thus, prophylactic cure or early treatment is desirable by local delivery to the inner ear. In this study, we examined a novel way of intratympanically delivered sustained nanoformulation by using crosslinked hybrid nanoparticle (cHy-NPs) in a thermoresponsive hydrogel i.e. thermogel that can potentially provide a safe and effective treatment towards the treatment-induced or drug-induced ototoxicity. The prophylactic treatment of the ototoxicity can be achieved by using two therapeutic molecules, Flunarizine (FL: T-type calcium channel blocker) and Honokiol (HK: antioxidant) co-encapsulated in the same delivery system. Here we investigated, FL and HK as cytoprotective molecules against cisplatin-induced toxic effects in the House Ear Institute - Organ of Corti 1 (HEI-OC1) cells and in vivo assessments on the neuromast hair cell protection in the zebrafish lateral line. We observed that cytotoxic protective effect can be enhanced by using FL and HK in combination and developing a robust drug delivery formulation. Therefore, FL-and HK-loaded crosslinked hybrid nanoparticles (FL-cHy-NPs and HK-cHy-NPs) were synthesized using a quality-by-design approach (QbD) in which design of experiment-central composite design (DoE-CCD) following the standard least-square model was used for nanoformulation optimization. The physicochemical characterization of FL and HK loaded-NPs suggested the successful synthesis of spherical NPs with polydispersity index < 0.3, drugs encapsulation (> 75%), drugs loading (~ 10%), stability (> 2 months) in the neutral solution, and appropriate cryoprotectant selection. We assessed caspase 3/7 apopototic pathway in vitro that showed significantly reduced signals of caspase 3/7 activation after the FL-cHy-NPs and HK-cHy-NPs (alone or in combination) compared to the CisPt. The final formulation i.e. crosslinked-hybrid-nanoparticle-embedded-in-thermogel was developed by incorporating drug-loaded cHy-NPs in poloxamer-407, poloxamer-188, and carbomer-940-based hydrogel. A combination of artificial intelligence (AI)-based qualitative and quantitative image analysis determined the particle size and distribution throughout the visible segment. The developed formulation was able to release the FL and HK for at least a month. Overall, a highly stable nanoformulation was successfully developed for combating treatment-induced or drug-induced ototoxicity via local administration to the inner ear.

Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions.

For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.

Characterization, DFT study and evaluation of antioxidant potentials of mycosporine-like amino acids (MAAs) in the cyanobacterium Anabaenopsis circularis HKAR-22.

The physiological parameters such as growth, Chl a content, and photosynthetic performance of the experimental cyanobacterium Anabaenopsis circularis HKAR-22 were estimated to evaluate the cumulative effects of photosynthetically active radiation (PAR) and ultraviolet (UV) radiation. Maximum induction of UV-screening molecules, MAAs, was observed under the treatment condition of PAR + UV-A + UV-B (PAB) radiations. UV/VIS absorption spectroscopy and HPLC-PDA detection primarily confirmed the presence of MAA-shinorine (SN) having absorption maxima (λmax) at 332.3 nm and retention time (RT) of 1.47 min. For further validation of the presence of SN, HRMS, FTIR and NMR were utilized. UV-stress elevated the in vivo ROS scavenging and in vitro enzymatic antioxidant capabilities. SN exhibited substantial and concentration-dependent antioxidant capabilities which was determined utilizing 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate (ABTS), ferric reducing power (FRAP) and superoxide radical scavenging assay (SRSA). The density functional theory (DFT) method using B3LYP energy model and 6-311G++(d,p) basis set was implied to perform the quantum chemical calculation to systematically investigate the antioxidant nature of SN. The principal pathways involved in the antioxidant reactions along with the basic molecular descriptors affecting the antioxidant potentials of a compound were also studied. The results favor the potential of SN as an active ingredient to be used in cosmeceutical formulations.

Density functional theory and enzyme studies support interactions between angiotensin receptor blockers and angiotensin converting enzyme-2: Relevance to coronavirus 2019.

The binding affinities and interactions between eight drug candidates, both commercially available (candesartan; losartan; losartan carboxylic acid; nirmatrelvir; telmisartan) and newly synthesized benzimidazole-N-biphenyltetrazole (ACC519T), benzimidazole bis-N,N'-biphenyltetrazole (ACC519T(2) and 4-butyl-N,N-bis([2-(2H-tetrazol-5-yl)biphenyl-4-yl]) methyl (BV6), and the active site of angiotensin-converting enzyme-2 (ACE2) were evaluated for their potential as inhibitors against SARS-CoV-2 and regulators of ACE2 function through Density Functional Theory methodology and enzyme activity assays, respectively. Notably, telmisartan and ACC519T(2) exhibited pronounced binding affinities, forming strong interactions with ACE2's active center, favorably accepting proton from the guanidinium group of arginine273. The ordering of candidates by binding affinity and reactivity descriptors, emerged as telmisartan > ACC519T(2) > candesartan > ACC519T > losartan carboxylic acid > BV6 > losartan > nirmatrelvir. Proton transfers among the active center amino acids revealed their interconnectedness, highlighting a chain-like proton transfer involving tyrosine, phenylalanine, and histidine. Furthermore, these candidates revealed their potential antiviral abilities by influencing proton transfer within the ACE2 active site. Furthermore, through an in vitro pharmacological assays we determined that candesartan and the BV6 derivative, 4-butyl-N,N0-bis[20-2Htetrazol-5-yl)bipheyl-4-yl]methyl)imidazolium bromide (BV6(K+)2) also contain the capacity to increase ACE2 functional activity. This comprehensive analysis collectively underscores the promise of these compounds as potential therapeutic agents against SARS-CoV-2 by targeting crucial protein interactions.

DMF-DMA catalyzed Synthesis, molecular docking, in-vitro, in-silico design, and binding free energy studies of novel thiohydantoin derivatives as antioxidant and antiproliferative agents targeting EGFR tyrosine kinase and aromatase cytochrome P450 enzyme.

A set of novels 2-thiohydantoin derivatives were synthesized and enaminone function was discussed at position 5 using DMFDMA catalyst which result in formation of pyrazole, isoxazole, benzoxazepine by using reagents such as hydrazine, hydroxylamine and 2-aminothiophenol. These newly synthesized compounds were evaluated for their antioxidant and antiproliferative activity. In vitro studies on the effect of 2-thiohydantoin on scavenging 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) confirmed the free radical scavenging and antioxidant activity of 2-thiohydantoin. The synthesized compounds show significant antioxidant activity. The in vitro antitumor activity of 2-thiohydantoin on MCF7 (breast) and PC3 cells (prostate) was evaluated using MTT assay. Some of the synthesized compounds show significant to moderate antiproliferative properties compared to reference drug erlotinib. Among all, compound 4a exhibit potent antitumor properties against MCF7 and PC3 cancer cell lines with IC50 = 2.53 ± 0.09 /ml & with IC50 = 3.25 ± 0.12 µg/ml respectively and has potent antioxidant activity with IC50 = 10.04 ± 0.49 µg/ml.

Synthesis, Characterization, X-ray Molecular Structure, Antioxidant, Antifungal, and Allelopathic Activity of a New Isonicotinate-Derived meso-Tetraarylporphyrin.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as elemental analysis and HR-MS. The structure of an n-hexane monosolvate has been determined by single-crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677, and C. tropicalis ATCC 64677) has been tested using the disk diffusion and microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

Green Synthesis of Silver Nanoparticles with Extracts from Kalanchoe fedtschenkoi: Characterization and Bioactivities.

In this work, the hexane, chloroform, and methanol extracts from Kalanchoe fedtschenkoi were utilized to green-synthesize silver nanoparticles (Kf1-, Kf2-, and Kf3-AgNPs). The Kf1-, Kf2-, and Kf3-AgNPs were characterized by spectroscopy and microscopy techniques. The antibacterial activity of AgNPs was studied against bacteria strains, utilizing the microdilution assay. The DPPH and H2O2 assays were considered to assess the antioxidant activity of AgNPs. The results revealed that Kf1-, Kf2-, and Kf3-AgNPs exhibit an average diameter of 39.9, 111, and 42 nm, respectively. The calculated ζ-potential of Kf1-, Kf2-, and Kf3-AgNPs were -20.5, -10.6, and -7.9 mV, respectively. The UV-vis analysis of the three samples demonstrated characteristic absorption bands within the range of 350-450 nm, which confirmed the formation of AgNPs. The FTIR analysis of AgNPs exhibited a series of bands from 3500 to 750 cm-1, related to the presence of extracts on their surfaces. SEM observations unveiled that Kf1- and Kf2-AgNPs adopted structural arrangements related to nano-popcorns and nanoflowers, whereas Kf3-AgNPs were spherical in shape. It was determined that treatment with Kf1-, Kf2-, and Kf3-AgNPs was demonstrated to inhibit the growth of E. coli, S. aureus, and P. aeruginosa in a dose-dependent manner (50-300 µg/mL). Within the same range, treatment with Kf1-, Kf2-, and Kf3-AgNPs decreased the generation of DPPH (IC50 57.02-2.09 µg/mL) and H2O2 (IC50 3.15-3.45 µg/mL) radicals. This study highlights the importance of using inorganic nanomaterials to improve the biological performance of plant extracts as an efficient nanotechnological approach.

Synthesis and characterization of novel carboxymethyl inulin derivatives bearing cationic Schiff bases with antioxidant potential.

This study aimed to enhance the antioxidant activity of carboxymethyl inulin (CMI) by chemical modification. Therefore, a series of cationic Schiff bases bearing heteroatoms were synthesized and incorporated into CMI via ion exchange reactions, ultimately preparing 10 novel CMI derivatives (CMID). Their structures were confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The radical scavenging activities and reducing power of inulin, CMI, and CMID were studied. The results revealed a significant enhancement in antioxidant activity upon the introduction of cationic Schiff bases into CMI. Compared to commercially available antioxidant Vc, CMID demonstrated a broader range of antioxidant activities across the four antioxidant systems analyzed in this research. In particular, CMID containing quinoline (6QSCMI) exhibited the strongest hydroxyl radical scavenging activity, with a scavenging rate of 93.60 % at 1.6 mg mL-1. The CMID bearing imidazole (2MSCMI) was able to scavenge 100 % of the DPPH radical at 1.60 mg mL-1. Furthermore, cytotoxicity experiments showed that the products had good biocompatibility. These results are helpful for evaluating the feasibility of exploiting these products in the food, biomedical, and cosmetics industries.

Structure-based discovery of novel piperidine-biphenyl-DAPY derivatives as non-nucleoside reverse transcriptase inhibitors featuring improved potency, safety, and selectivity: From piperazine-biphenyl-DAPYs to piperidine-biphenyl-DAPYs.

Starting from our previously reported nonnucleoside reverse transcriptase inhibitor (NNRTI, 3), continuous efforts were made to enhance its potency and safety through a structure-based drug design strategy. This led to the discovery of a series of novel piperidine-biphenyl-diarylpyrimidines (DAPYs). Compound 10p, the most active compound in this series, exhibited an EC50 value of 6 nM against wide-type HIV-1 strain, which was approximately 560-fold more potent than the initial compound 3 (EC50 = 3.36 µM). Furthermore, significant improvements were observed in cytotoxicity and selectivity (CC50 > 202.17 µM, SI > 33144) compared to compound 3 (CC50 = 14.84 µM, SI = 4). Additionally, compound 10p demonstrated increased inhibitory activity against clinically mutant virus strains (EC50 = 7-63 nM). Further toxicity evaluation revealed that compound 10p exhibited minimal CYP enzyme and hERG inhibition. Importantly, single-dose acute toxicity testing did not result in any fatalities or noticeable pathological damage in mice. Therefore, compound 10p can be regarded as a lead candidate for guiding further development of biphenyl-diarylpyrimidine NNRTIs with favorable druggability for HIV therapy.

N-methylmorpholine incorporation into the structure of biphenyl leads to the bioactive inhibitor of PD-1/PD-L1 interaction.

We present new small-molecular probes targeting the human PD-L1 protein. The molecules were designed by incorporating a newly discovered N-methylmorpholine substituent into a known biphenyl-based structure. Four prototype derivatives of 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carbonitrile (STD4), comprising a morpholine substituent fused with a biphenyl core at different orientations were first verified for their potential binding to PD-L1 using the molecular docking method. A more favorable 7-phenyl derivative of STD4 was then equipped with an amide bond, pyridine, and either a tris(hydroxymethyl)aminomethane or serinol tail leading to two final molecules. Among them, compound 1c showed activity in three bioassays, i.e., the homogenous time-resolved fluorescence (HTRF) assay, immune checkpoint blockade (ICB) assay, and T-cell activation (TCA) assay. Our work shows that morpholine can substitute for dioxane and becomes a promising component in PD-L1-targeting molecules. This finding unlocks new avenues for optimizing PD-L1-targeting compounds, presenting exciting prospects for future developments in this field.

Redox/pH Dual-Responsive Fluorescent Nanoparticles for Intelligent Pesticide Release and Visualization in Gray Mold Disease Synergistic Control.

An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea (B. cinerea). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.

Discovery of Biphenyl Derivatives to Target Hsp70-Bim Protein-Protein Interaction in Chronic Myeloid Leukemia by Scaffold Hopping Strategy.

Hsp70-Bim protein-protein interaction (PPI) is the most recently identified specific target in chronic myeloid leukemia (CML) therapy. Herein, we developed a new class of Hsp70-Bim PPI inhibitors via scaffold hopping of S1g-10, the most potent Hsp70-Bim PPI inhibitor thus far. Through structure-activity relationship (SAR) study, we obtained a biphenyl scaffold compound JL-15 with a 5.6-fold improvement in Hsp70-Bim PPI suppression (Kd = 123 vs 688 nM) and a 4-fold improvement in water solubility (29.42 vs 7.19 µg/mL) compared to S1g-10. It maintains comparable apoptosis induction capability with S1g-10 against both TKI-sensitive and TKI-resistant CML cell lines in an Hsp70-Bim-dependent manner. Additionally, through SAR, 1H-15N TRSOY-NMR, and molecular docking, we revealed that Lys319 is a "hot spot" in the Hsp70-Bim PPI interface. Collectively, these results provide a novel chemical scaffold and structural insights for the rational design of Hsp70-Bim PPI inhibitors.

Antioxidant potentials of extracts from different parts of Clinacanthus nutans (Burm. f.) Lindau.

The research aimed to explore the antioxidant potential of extracts from different parts of Clinacanthus nutans growing in Vietnam, a member of the Acanthaceae family. The plant's roots, stem and leaves were extracted using 96% ethanol. The antioxidant actions of these extracts were evaluated by DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay on thin-layer plates and 96 well plates. The extract with the most potent activity was applied for distribution extraction with solvents with different polarities, including dichloromethane, ethyl acetate and water. Dry column vacuum chromatography was utilized to obtain the most antioxidant-potent extract fractions. The stem extract had the lowest IC50 value of 6.85µg/mL, showing the most potent antioxidant activity. The ethyl acetate fraction from the stem extract expressed the lowest IC50 value of 9.67µg/mL. Meanwhile, fraction 5, separated from the ethyl acetate fraction of the stem extract, had the lowest IC50 value of 9.89µg/mL. In conclusion, the extracts from different parts of Clinacanthus nutans all expressed antioxidant action at different levels, in which the stem extract, the ethyl acetate fraction and fraction 5 from the ethyl acetate fraction displayed the most effective actions. These findings highlight the promising potential of Clinacanthus nutans in treating oxidative stress-associated diseases, inspiring further research and exploration in this area.

Synthesis and Antioxidant Activity of N-Benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine Oxides.

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a-d are reported herein. The nitrones 10a-d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS•+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5-81% after 20 min; 79-96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTS•+ were not significant, since all tested compounds 10a-d showed negligible activity (8-46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC50 = 10 µM).

Novel composite fatty acid vesicles-in-Pluronic lecithin organogels for enhanced magnolol delivery in skin cancer treatment.

A novel composite carrier composed of Pluronic lecithin organogels and fatty acid vesicles was used to enhance the stability and facilitate the topical delivery of a natural bioactive drug, magnolol (Mag), for treatment of skin cancer. Jojoba oil was incorporated in the organogel (OG) base to provide a synergistic effect in treatment of skin cancer. The organoleptic properties, rheological behavior, morphology, and drug content of the OG formulations were investigated with emphasis on the impact of vesicle loading on the OG characteristics. The effect of OG on Mag release and ex-vivo permeation studies were evaluated and compared to free Mag in OG. The biological anti-tumor activity of the OG formulae was assessed using a skin cancer model in mice. All OG formulations exhibited uniform drug distribution with drug content ranging from 92.22 ± 0.91 to 100.45 ± 0.77 %. Rheological studies confirmed the OG shear-thinning flow behavior. Ex-vivo permeation studies demonstrated that the permeation of Mag from all OG formulations surpassed that obtained with free Mag in the OG. The anti-tumor activity studies revealed the superior efficacy of 10-hydroxy-decanoic acid (HDA)-based vesicles incorporated in OG formulations in mitigating 7,12- dimethylbenz(a)anthracene (DMBA)-induced skin cancer, thereby offering a promising platform for the local delivery of Mag.

Solidification of deep eutectic solvent containing fimasartan through wet impregnation and exploration of flow attributes by modified SeDeM-SLA expert system.

The solidification of deep eutectic solvent (DES) through wet impregnation techniques on inert solid carriers is an interesting approach that offers better processing attributes and excellent stability. Herein, DES of Fimasartan (FS) was developed to improve its solubility and bioavailability. The selected DES-FS was solidified by wet impregnation method employing Nesulin US2 and Aerosil 200. The SeDeM-SLA (solid-liquid adsorption) system was employed to investigate flow attributes of solidified DES-FS. Further, the selected solidified DES-FS (A) was characterized by Fourier transforms infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM). The DES comprising Choline Chloride (ChCl): Glycerol (Gly) (1:3) revealed maximum drug solubility (35.6 ± 2.2 mg/mL) and thus opted for solidification. Solidification through wet impregnation was employed using 1:0.5 ratios (DES-FS to carriers). The Index of Good Flow (IGF) value was calculated from the SeDeM-SLA expert system, which indicates the better flow characteristics of solidified DES-FS, particularly with Neusilin US2 [SDES-FS (A)]. The solid-state evaluation data of SDS-FS (A) suggested a transition of FS to an amorphous form, resulting in an increment in solubility and dissolution. A similar trend was reported in the in vivo pharmacokinetic study, which indicated a 2.9 folds increment in the oral bioavailability of FS. Furthermore, excellent stability, i.e., a shelf life of 28.44 months, reported by SDES-FS (A) in accelerated stability studies, suggests better formulation perspectives. In a nutshell, the present study evokes the potentiality of performing solidification through wet impregnation and successful implementation of the SeDeM-SLA expert model, which could find wide applications in pharmaceutical science.

Antioxidant inactivated yeast: High potential of non-Saccharomyces specific metabolome.

Understanding the contribution of new natural sources of antioxidant compounds to the stability of wines is of great interest in a context of reduction of sulfites. Here, we investigated the antioxidant potential of selected inactivated non-Saccharomyces yeast (INSY) along with related chemical fingerprints, using combined untargeted UHPLC-Q-ToF MS and DPPH analyses. 4 INSY species were compared to a reference inactivated Saccharomyces cerevisiae yeast (ISY) selected for its high antioxidant capacity. Our results show that, all the INSY can accumulate GSH during the specific production process with yields ranging from +170 % to +360 % compared to the corresponding classical production process. The principal component analysis of the 3511 ions detected by UHPLC-Q-ToF-MS clearly grouped INSY by species, independently of the production process. One INSY exhibited equivalent antioxidant capacity to the control ISY, but with a GSH concentration four times lower (4.73 ± 0.09 mg/g against 20.95 ± 0.34 mg/g, respectively). 73 specific ions presenting strong and significant spearman correlation (rho < -0.6, p-value < 0.05) with the DPPH scores, clustered the most antioxidant INSY and the control Saccharomyces in different groups, indicating that the antioxidant capacity of these two products should be driven by different pools of compounds. These results point out that, GSH alone is not relevant to explain the antioxidant capacity of INSY soluble fractions and other more reactive compounds must be considered, which opens an avenue for the selection new species with great enological potential.

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach.

Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki-Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98-100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.

Quality Evaluation of Lonicerae Flos Produced in Southwest China Based on HPLC Analysis and Antioxidant Activity.

Lonicera macranthoides, the main source of traditional Chinese medicine Lonicerae Flos, is extensively cultivated in Southwest China. However, the quality of L. macranthoides produced in this region significantly varies due to its wide distribution and various cultivation breeds. Herein, 50 Lonicerae Flos samples derived from different breeds of L. macranthoides cultivated in Southwest China were collected for quality evaluation. Six organic acids and three saponin compounds were quantitatively analyzed using HPLC. Furthermore, the antioxidant activity of a portion of samples was conducted with 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging experiments. According to the quantitative results, all samples met the quality standards outlined in the Chinese Pharmacopoeia. The samples from Guizhou, whether derived from unopened or open wild-type breeds, exhibited high quality, while the wild-type samples showed relatively significant fluctuation in quality. The samples from Chongqing and Hunan demonstrated similar quality, whereas those from Sichuan exhibited relatively lower quality. These samples demonstrated significant abilities in clearing ABTS and DPPH radicals. The relationship between HPLC chromatograms and antioxidant activity, as elucidated by multivariate analysis, indicated that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C are active components and can serve as Q-markers for quality evaluation.