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.

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.

Different wavelengths of LED irradiation promote secondary metabolite production in Pycnoporus sanguineus for antioxidant and immunomodulatory applications.

Pycnoporus sanguineus is a fungus of the phylum Basidiomycota that has many applications in traditional medicine, modern pharmaceuticals, and agricultural industries. Light plays an essential role in the metabolism, growth, and development of fungi. This study evaluated the mycelial growth and antioxidant and anti-inflammatory activities in P. sanguineus fermentation broth (PFB) cultured under different wavelengths of LED irradiation or in the dark. Compared to the dark cultures, the dry weight of mycelia in red- and yellow-light cultures decreased by 37 and 35% and the yields of pigments increased by 30.92 ± 2.18 mg and 31.75 ± 3.06 mg, respectively. Compared with the dark culture, the DPPH free radical scavenging ability, ABTS+ free radical scavenging capacity, and reducing power of yellow-light cultures increased significantly, and their total phenolic content peaked at 180.0 ± 8.34 µg/mL. However, the reducing power in blue-light cultures was significantly reduced, though the total phenol content did not vary with that of dark cultures. In LPS- and IFN-γ-stimulated RAW 264.7 cells, nitrite release was significantly reduced in the red and yellow light-irradiated PFB compared with the dark culture. In the dark, yellow-, and green-light cultures, TNF-α production in the inflamed RAW 264.7 cells was inhibited by 62, 46, and 14%, respectively. With red-, blue-, and white-light irradiation, TNF-α production was significantly enhanced. Based on these results, we propose that by adjusting the wavelength of the light source during culture, one can effectively modulate the growth, development, and metabolism of P. sanguineus.

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.

Semisynthesis and biological evaluation of novel honokiol thioethers against colon cancer cells HCT116 via inhibiting the transcription and expression of YAP protein.

Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC50 value of 6.1 µmol/L, superior to the reference drug 5-fluorouracil (IC50: 9.63 ± 0.27 µmol/L). The structure-activity relationships (SARs) indicated that the introduction of -(4-NO2)Ph, 3-pyridyl, -(2-F)Ph, -(4-F)Ph, -(3-F)Ph, -(4-Cl)Ph, and -(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.

Structure-guided design of novel biphenyl-quinazoline derivatives as potent non-nucleoside reverse transcriptase inhibitors featuring improved anti-resistance, selectivity, and solubility.

In pursuit of enhancing the anti-resistance efficacy and solubility of our previously identified NNRTI 1, a series of biphenyl-quinazoline derivatives were synthesized employing a structure-based drug design strategy. Noteworthy advancements in anti-resistance efficacy were discerned among some of these analogs, prominently exemplified by compound 7ag, which exhibited a remarkable 1.37 to 602.41-fold increase in potency against mutant strains (Y181C, L100I, Y188L, F227L + V106A, and K103N + Y181C) in comparison to compound 1. Compound 7ag also demonstrated comparable anti-HIV activity against both WT HIV and K103N, albeit with a marginal reduction in activity against E138K. Of significance, this analog showed augmented selectivity index (SI > 5368) relative to compound 1 (SI > 37764), Nevirapine (SI > 158), Efavirenz (SI > 269), and Etravirine (SI > 1519). Moreover, it displayed a significant enhancement in water solubility, surpassing that of compound 1, Etravirine, and Rilpivirine. To elucidate the underlying molecular mechanisms, molecular docking studies were undertaken to probe the critical interactions between 7ag and both WT and mutant strains of HIV-1 RT. These findings furnish invaluable insights driving further advancements in the development of DAPYs for HIV therapy.

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.

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.

Fishing antioxidant 4-hydroxycoumarin derivatives: synthesis, characterization, and in vitro assessments.

Coumarins represent a diverse class of natural compounds whose importance in pharmaceutical and agri-food sectors has motivated multiple novel synthetic derivatives with broad applicability. The phenolic moiety in 4-hydroxycoumarins underscores their potential to modulate the equilibrium between free radicals and antioxidant species within biological systems. The aim of this work was to assess the antioxidant activity of 18 4-hydroxycoumarin coumarin derivatives, six of which are commercially available and the other 12 were synthesized and chemically characterized and described herein. The 4-hydroxycoumarins were prepared by a two steps synthetic strategy with satisfactory yields. Their antioxidant potential was evaluated through three in vitro methods, two free radical-scavenging assays (DPPH• and ABTS•+) and a metal chelating activity assay. Six synthetic coumarins (4a, 4g, 4h, 4i, 4k, 4l) had a scavenging capacity of DPPH• higher than butylated hydroxytoluene (BHT) (IC50 = 0.58 mmol/L) and compound 4a (4-hydroxy-6-methoxy-2 H-chromen-2-one) with an IC50 = 0.05 mmol/L outperformed both BHT and ascorbic acid (IC50 = 0.06 mmol/L). Nine hydroxycoumarins had a scavenging capacity against ABTS•+ greater (C3, 4a, 4c) or comparable (C1, C2, C4, C6, 4g, 4l) to Trolox (IC50 = 34.34 µmol/L). Meanwhile, the set had a modest ferrous chelation capacity, but most of them (C2, C5, C6, 4a, 4b, 4h, 4i, 4j, 4k, 4l) reached up to more than 20% chelating ability percentage. Collectively, this research work provides valuable structural insights that may determine the scavenging and metal chelating activity of 4-hydroxycoumarins. Notably, substitutions at the C6 position appeared to enhance scavenging potential, while the introduction of electron-withdrawing groups showed promise in augmenting chelation efficiency.

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.

Extraction of Lentinus Edodes Polysaccharides with Ultrasound Enhanced with Deep Eutectic Solvent and Their Structural Characterization and Antioxidant Activity.

Ultrasound extraction (UE) enhanced with deep eutectic solvent (DES) was used to extract Lentinus edodes polysaccharides. Box-Behnken design (BBD) was applied to investigate the influences of water content (10-90 %), solid-liquid solvent (1 : 10-1 : 50 g/mL), time (4-12 min), temperature (40-80 °C) and ultrasonic power (100-500 W) on the yield of Lentinus edodes polysaccharides. The optimal extraction conditions were ultrasonic power of 300 W, extraction time of 8 min, water content of 80 %, a solid-liquid ratio of 1 : 30 g/mL and a temperature of 60 °C, respectively. The highest extraction yield of Lentinus edodes polysaccharide was 10.17 % under optimal conditions. The results of FT-IR, SEM, and monosaccharide composition confirmed that the extracts possessed the characteristics of polysaccharides. In addition, the polysaccharides obtained with the UE enhanced with DES method exhibited higher antioxidant activities than the polysaccharides extracted with the UE method and HWE method. This extraction method can further expand the production efficiency and structural diversity of Lentinus edodes polysaccharides and meet the supply and demand relationship. It can be foreseen that this method can be applied to the extraction of more active substances.

Delivery Strategies, Structural Modification, and Pharmacological Mechanisms of Honokiol: A Comprehensive Review.

Honokiol (HK) is a traditional Chinese herbal bioactive compound that originates mainly from the Magnolia species, traditionally used to treat anxiety and stroke, as well as alleviation of flu symptoms. This natural product and its derivatives displayed diverse biological activities, including anticancer, antioxidant, anti-inflammatory, neuroprotective, and antimicrobial activities. However, its poor bioavailability and pharmacological activity require primary consideration in the development of HK-based drugs. Recent innovative HK formulations based on the nanotechnology approach allowed for improvement in both bioavailability and therapeutic efficacy. Chemical derivation and drug combination are also effective strategies to ameliorate the drawbacks of HK. In recent years, studies on HK derivatives and compositions have made great progress in the treatment of cancer, inflammation, bacterial infection, cardiovascular, and cerebrovascular diseases, demonstrating better activity than HK. The objective of this review is an examination of the recent developments in the field of pharmacological activity of HK and its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials in HK are also summarized.

Exploring the Pharmacognostical and Phytochemical Profiles of Aqueous Extracts of Kalanchoe.

The use of plants for medicinal purposes has a long history, however it is desirable a continuous evaluation seeking for complementary scientific evidences for their safe application. Species within the Kalanchoe genus are often referred to as "miracle leaf" due to their remarkable healing properties. Traditionally, these plants have been used to treat infections, inflammation, and cancer. Despite their widespread use, the identification of their active components remains incomplete. This study aimed to differentiate K. crenata (KC), K. marmorata (KM), and K. pinnata (KP) by conducting detailed histochemical and phytochemical analyses, and to assess their antioxidant capabilities. The investigation revealed significant differences between the species, highlighting the variability in phenolic (PC) and flavonoid contents (FC) and their distinct antioxidant effects. The KM demonstrated the greatest results (PC: 59.26±1.53 mgEqGA/g; FC: 12.63±0.91 mgEqCQ/g; DPPH⋅ (IC50): 110.66 ug/mL; ABTS⋅+ (IC50): 26.81 ug/mL; ORAC: 9.65±0.75 mmolTE) when compared to KC and KP. These findings underscore a new reference for research within the Kalanchoe genus.

Anti-Inflammatory and Antioxidant Effects of Rosmarinic Acid Trimetallic (Cu0.5Zn0.5Fe2O4) Nanoparticles.

Newly, green metallic-nanoparticles (NPs) have received scientists' interest due to their wide variable medicinal applications owned to their economical synthesis and biologically compatible nature. In this study, we used rosmarinic acid (RosA) to prepare Cu0.5Zn0.5FeO4 NPs and later encapsulated them using PEG polymer. Characterization of NPs was done using the XRD method and SEM imaging. Further, we explored the encapsulated NPs for anti-inflammatory properties by downregulating the expression of pro-inflammatory cytokines mRNA in LPS-stimulated Raw 264.7 cells. Besides, employing DPPH, NO and ABTS radical scavenging assays to examine the antioxidant activity of the synthesized Cu0.5Zn0.5FeO4 NPs. Cu0.5Zn0.5FeO4 NPs revealed moderate antioxidant activity by scavenging DPPH and nitric oxide. We demonstrated that the NPs showed high potential anti-inflammatory activity by suppressing the mRNA and protein levels of pro-inflammatory cytokines in a dose-dependent manner, in LPS-induced Raw 264.7 cells. To our best knowledge, this is the first report where RosA was found to be a suitable phyto source for the green synthesis of Cu0.5Zn0.5FeO4 NPs and their in vitro anti-inflammatory and antioxidant effects. Taken together, our findings suggest that the RosA is a green resource for the eco-friendly synthesis of Cu0.5Zn0.5FeO4/PEG NPs, which further can be employed as a novel anti-inflammatory therapeutic agent.

One Pot Synthesis and Biological Activity Studies of New Spirooxindoles.

This article reports one-pot synthesis of ten novel spirooxindoles using 5-methyl-2-thiohydantoin, isatin derivatives, and malononitrile in good to high yields (65-90 %). The structures of the synthesized compounds were deduced by 1H-NMR, 13C NMR, FT-IR, and Mass spectral data. The antibacterial activity of the compounds was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) based on the Kirby-Bauer method. According to the obtained data, the synthesized compounds show more activity against Gram-positive bacteria than Gram-negative bacteria. Also, the antioxidant activity of these compounds was measured using the DPPH radical scavenging test method, which showed good to excellent activity (59.65-94.03 %). Among them, the chlorinated derivatives (4 f-j) exhibited more antioxidant activity (84.85-94.03 %) than the other compounds (4 a-e) (56.65-74.4 %) and even ascorbic acid as a standard antioxidant compound (82.3 %).

New penta-Coordinated Cadmium(II) Complexes: Synthesis, Characterization, Thermal, Antimicrobial, Antioxidant and Cytotoxicity Properties.

In this paper, a new tridentate Schiff base ligand (L) with nitrogen donor atoms and its cadmium(II) complexes with the general formula of CdLX2 (X=Cl-, Br-, I-, SCN-, N3 -, NO3 -) have been synthesized and characterized by physical and spectral (FT/IR, UV-Vis, Mass, and 1H, 13C NMR spectroscopies) methods. Also nano-structured cadmium chloride and bromide complexes were synthesized by sonochemical method and then used to prepare nanostructured cadmium oxide confirmed by XRD and SEM techniques. Thermal behavior of the compounds was studied in the temperature range of 25 to 900 °C under N2 atmosphere at a heating rate of 20 °C/ min. Moreover, thermo-kinetic activation parameters of thermal decomposition steps were calculated according to the Coats-Redfern relationship. Antimicrobial activities of the synthesized compounds against two gram-positive and two gram-negative bacteria such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and two fungi of Candida albicans and Aspergillus niger were investigated by well diffusion method. SEM technique was used to monitor the morphological changes of the bacteria treated with the compounds. The 2,2-Diphenyl-1-picrylhydrazyl(DPPH) and the ferric reducing antioxidant power (FRAP) methods were used to evaluate the antioxidant ability of the ligand and its cadmium(II) complexes. In final, the cytotoxicity properties of the ligand and some cadmium(II) complexes against PC3 cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) bioassay and nitric oxide (NO) level measurement. The morphological changes of prostate cancer (PC3) cells due to treatment with the ligand and its complexes confirmed their anticancer effectiveness.

Novel N-pyrocatechoyl and N-pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity.

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress-associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N-pyrocatechoyl and N-pyrogalloyl hydrazones (N-PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N-PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT-116 cells and healthy fibroblasts MRC-5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone-type hybrids encouraged investigations on G+ and G- bacterial strains, which revealed the antibacterial potency of several N-PYRs. These findings highlighted the N-PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.

Plant-assisted green preparation of silver nanoparticles using leaf extract of Dalbergia sissoo and their antioxidant, antibacterial and catalytic applications.

Plant-mediated preparation of silver nanoparticles (AgNPs) is thought to be a more economical and environmentally benign process in comparison to physical and chemical synthesis methods. In the present study, the aqueous leaf extract of Dalbergia sissoo was prepared and utilized to reduce silver ion (Ag+) during the green synthesis of silver nanoparticles (DL-AgNPs). The formation of DL-AgNPs was verified using UV-Vis spectra, exhibiting the surface plasmon resonance (SPR) band at around 450 nm. FT-IR analysis revealed the kinds of phytochemicals that serve as reducing and capping agents while DL-AgNPs are being synthesized. Analysis of scanning electron microscope (SEM) and high-resolution transmission electron microscopy (HR-TEM) images verified the development of spherical and oval-shaped DL-AgNPs, with sizes ranging from 10 to 25 nm. The stability and particle size distribution of synthesized DL-AgNPs were ensured by zeta potential and DLS (dynamic light scattering) investigations. Additionally, X-ray diffraction (XRD) analysis confirmed the crystalline nature of DL-AgNPs. In antioxidant experiments, DL-AgNPs demonstrated significant scavenging capacities of DPPH and ABTS radicals with EC50 values of 51.32 and 33.32 µg/mL, respectively. The antibacterial activity of DL-AgNPs was shown to be significant against harmful bacteria, with a maximum zone of inhibition (21.5 ± 0.86 mm) against Staphylococcus aureus. Furthermore, DL-AgNPs exhibited effective catalytic activity to degrade environment-polluting dyes (methylene blue, methyl orange, and Congo red) and toxic chemicals (p-nitrophenol). The results of all these studies suggested that DL-AgNPs made from the leaf extract of Dalbergia sissoo have merit for application in the environmental and biomedical fields.

Simultaneous separation and determination of seven biphenyl cyclooctene lignans in Schisandra chinensis and its preparations by micellar electrokinetic chromatography with dual organic solvent system.

INTRODUCTION: Gomisin is a natural dibenzo cyclooctene lignan, which is mainly derived from the family Magnoliaceae. It has anti-inflammatory, antioxidant, anti-tumor, anti-aging, and hypoglycemic effects. Gomisins play important roles as medicines, nutraceuticals, food additives, and cosmetics. OBJECTIVE: The objective of this study is to establish a micellar electrokinetic chromatography (MEKC) method for simultaneous separation and determination of seven biphenyl cyclooctene lignans (Gomisin D, E, G, H, J, N, and O) in Schisandra chinensis and its preparations. METHODS: The method was optimized by studying the effects of the main parameters on the separation. The method has been validated and successfully applied to the determination of seven Gomisins in S. chinensis and its preparations. RESULTS: In the separation system, the running buffer was composed of 20 mM Na2HPO4, 8.0 mM sodium dodecyl sulfate (SDS), 11% (v/v) methanol, and 6.0% (v/v) ethanol. A diode array detector was used with a detection wavelength of 230 nm, a separation voltage of 17 kV, and an operating temperature of 25°C. Under this condition, the seven analytes were separated at baseline within 20 min, and a good linear relationship was obtained with correlation coefficient ranging from 0.9919 to 0.9992. The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) ranged from 0.8 to 0.9 µg/mL and from 2.6 to 3.0 µg/mL, respectively. The recovery rate was between 99.1% and 102.5%. CONCLUSION: The experimental results indicated that this method is suitable for the separation and determination of seven Schisandra biphenyl cyclooctene lignan compounds in real samples. At the same time, it provides an effective reference for the quality control of S. chinensis and its preparations.

Improving cellular uptake and synergetic anti-tumor effects of magnolol and Brucea javanica oil through self-microemulsion.

OBJECTIVE: Magnolol (MG) and Brucea javanica (L.) Merr. oil (BJO) possess synergetic anti-tumor effects, but have poor water solubility and stability, which results in low oral bioavailability. SIGNIFICANCE: The MG loaded self-microemulsion drug delivery system (MG-SMDDS) with BJO as oil phase component was utilized to improve the cellular uptake and synergetic anti-tumor effects. METHODS: Compatibility study and pseudoternary phase diagram (PTPD) were respectively employed to screen for the composition and proportion of oil phase in the formulation. Central composite design-effect surface method was applied to optimize proportion of each formulation condition. The droplet size, ζ-potential, colloid stability, encapsulation rate (ER) and in vitro dissolution rate of MG-SMDDS were evaluated. Furthermore, cellular uptake and cytotoxicity of the microemulsion on HepG2 cells were assessed. RESULTS: The optimal composition of MG-SMDDS was: MG (9.09%), castor oil (7.40%), BJO (2.47%), Cremophor EL 35 (54.04%) and 1, 2-propanediol (27.01%). The MG-SMDDS exhibited satisfactory droplet size, ζ-potential, colloid stability and ER, as well as faster dissolution rate than free MG. More importantly, SMEDDS containing BJO could enhance the cellular uptake and cytotoxicity of free BJO and free MG on tumor cells. CONCLUSIONS: The BJO self-microemulsion delivery technique can provide an idea for design of oral delivery vehicles based on BJO.