Series Of Esters Research Articles

Synthesis of antibiofilm (1R,4S)-(-)-fenchone derivatives to control Pseudomonas syringae pv. tomato.

Biofilm plays a crucial role in Pseudomonas syringae pv. tomato (Pst) infection. We identified (1R,4S)-(-)-fenchone (FCH) as the most potent antibiofilm agent against Pst among 39 essential oil compounds. Subsequently, we synthesized a series of FCH oxime ester and acylhydrazine derivatives to explore more potent derivatives. II3 was screened out as the most potent derivative, exhibiting a minimal biofilm inhibitory concentration of 60 μg mL-1 and a lowest concentration with maximal biofilm inhibition (LCMBI) of 200 μg mL-1, lower than those of FCH (80 and 500 μg mL-1, respectively). II3 and FCH showed minimum inhibitory concentration values >1000 μg mL-1 and similar maximal biofilm inhibition extents of 48.7% and 49.5% at their respective LCMBIs, respectively. Meanwhile, neither of them influenced cell viability or the activity of metabolic enzymes at their respective LCMBIs. II3 at its LCMBI significantly reduced biofilm thickness, extracellular polysaccharide content, and pectinase and cellulase production indices. In vivo assay results indicated that II3 could preventatively reduce the bacterial contents in tomato leaves at its LCMBI, and when combined with kasugamycin (KSG) (10 μg mL-1), II3 achieved the same level of bacterial reduction as the sole application of KSG (70 μg mL-1), thereby reducing the required dosage of KSG. Mechanistic studies demonstrated that II3 can down-regulate biofilm-related genes and inhibit PsyR/PsyI quorum sensing system, which differs from the bactericidal mechanisms. These results underscore the potential of II3 as an antibiofilm agent for the control of Pst or FCH as a promising natural candidate for future in-depth optimization. © 2024 Society of Chemical Industry.

Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.

Design, Synthesis, and Screening for Anticancer and Antimicrobial Activities of New Dihydropyridine‐Anchored Pyrazole and 1,2,3‐Triazole Hybrids

AbstractTwo new libraries of diethyl and dimethyl dihydropyridines‐based pyrazole and 1,2,3‐triazole hybrids (7a–g and 7h–n) were synthesized via a series of reactions involving click chemistry, pyrazole synthesis, and multicomponent reaction. All the new compounds were screened for their in vitro anticancer activity and antimicrobial activities. The 4‐chloro substituted analogue (7i) in dimethyl ester series showed an excellent activity against all three, namely, human breast adenocarcinoma (MCF‐7), human cervical cancer (HeLa), and human breast cancer triple‐positive (BT‐474) cell lines with IC50 values of 0.119 ± 0.58 µM, 0.135 ± 0.13 µM, and 0.163 ± 0.31 µM, respectively compared to abemaciclib. Molecular docking studies performed on the best active compound 7i against crystal structure of CDK6 revealed its best binding score and interactions. Additionally, these libraries were screened for their antimicrobial activities and determined their MIC. Compounds with ─Cl (7b), ─OMe (7d), ─Me (7a) substitution, and without substitution (7e) significantly showed better MIC values in comparison to ampicillin and nystatin.

Prognostic significance of plasma molecular lipid species in coronary artery disease patients: A prospective cohort study

Abstract Background Circulating plasma lipids are vital indicators for quantifying coronary artery disease (CAD) risk, yet traditional biomarkers like LDL, HDL, and triglycerides often exhibit limited predictive capacity. Advancements in lipidomics have identified novel molecular constituents with the potential to improve prognostication in CAD patients. However, the prognostic value of lipidomics for long-term mortality has not yet been investigated. Objective In our study, which was part of the European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis (ATHEROREMO), we aimed to investigate the predictive value of specific molecular lipid species for long-term mortality. Methods We utilized data from the 581 CAD patients enrolled in the ATHEROREMO clinical imaging study, who were admitted for either diagnostic coronary angiography or percutaneous coronary intervention. We measured a series of serum lipid species, comprising ceramides (Cer) and cholesteryl esters (CE), by mass spectrometry-based shotgun lipidomics. Long-term all-cause mortality follow-up was conducted in 2022 via the Civil Registry. We used the Kaplan-Meier method and multivariable Cox-proportional hazards regression (correction for age, sex, cardiac risk factors, statin use, hypercholesterolemia, and angiography indication) to assess survival distributions and associations with all-cause mortality. Results Mean age was 61.5 years (IQR: 53.5-61.5), 75% were male. A total of 55% patients were diagnosed with acute coronary syndrome (ACS) and 45% with stable angina pectoris (SAP). During a median follow-up of 11 years (IQR: 10.1-13.4) 179 patients died. Five molecular lipid species (two cholesteryl esters, one ceramide and two ceramide ratios) correlated with mortality (see Table). As an example, Figure 1 demonstrates a clear survival difference between patients with Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio below versus above the median. Findings were consistent for ACS and SAP. Conclusion Our study demonstrates the prognostic value of specific cholesteryl esters, ceramides and ceramide ratios for 11-year mortality in patients with CAD. To the best of our knowledge, this is the longest follow-up study so far within this domain.Table.Lipid molecule and Mortality 11-yFig.1 Kaplan Meier Ceramide ratio

Intermolecular 1,2-Aminoboration of Alkynes and the Critical Role of Electron-Rich Alkynes.

The intramolecular 1,2-aminoboration of alkynes by aminoboranes is rare and invariably requires a catalyst to proceed, while the intermolecular aminoboration of alkynes is yet entirely unknown. Through an exploration of the significance of electronics in alkynes for activating the B-N σ-bond of aminoboranes, we demonstrate in this work the first intermolecular 1,2-aminoboration of alkynes. These reactions employ a series of (amino)dihaloboranes and aminoboronic esters, mild reaction conditions, and no catalysts, yielding syn-addition alkene products with incorporation of two crucial functionalities: amino and boryl. While highly electron-rich examples can afford the aminoborated products (Z)-2-borylethenamines, other alkynes, including unactivated and less electron-rich examples, do not lead to the corresponding aminoborated products due to the fundamental impediment that the reactions are significantly endergonic.

C═N Bond Ozonolysis and β-Scission: A Breakthrough Approach to the Synthesis of ω-Functionalized Compounds from Carbonyl Derivatives.

This work discloses a two-step, one-pot approach to ω-functionalized esters via cleavage of the alicyclic fragment of cycloalkanone semicarbazones. This approach is based on a combination of the synthesis of various alkoxyhydroperoxides via cycloalkanone semicarbazone ozonolysis and in situ interaction of these peroxides with transition metal salts, leading to cleavage of the aliphatic cycle and subsequent ω-functionalized ester formation. A broad series of ω-halogen or pseudohalogen esters have been successfully synthesized in yields ranging from 23 to 73% per starting semicarbazone. A major advantage of the approach is the ability to use different cycloalkanone semicarbazones, including those with large cycles and substituents in them. The possibility of carrying out ozonolysis in the presence of various alcohols makes it possible to obtain the corresponding esters of ω-substituted carboxylic acids.

Light-Up Fluorescence and Circularly Polarized Luminescence in Achiral Interlocked Framework via Adaptive Lone Pair-π Interaction Confinement.

Interactions between lone pairs and aromatic π systems are significant across biology and self-assembled materials. Herein, employing an achiral confinement metal-organic framework (MOF) encapsulates guest molecules, it is successfully realized that lone pair (lp)-π interaction induces fluorescence "turn-on" and circularly polarized luminescence for the first time. The MOFs synthesized based on naphthalenediimide show nearly non-emissive, which can be light-up by introducing acetone or ester guests containing lone pairs-π interaction. Furthermore, the introduction of a series of lp-rich chiral esters induces supramolecular chirality as well as circularly polarized luminescence in achiral MOFs, while also observing chiral adaptability. This work first demonstrates the luminescence and chiral induction via lone pair electrons-π interactions, presenting a fresh paradigm for the advancement of chiroptical materials.

Green biocatalytic synthesis of (hydroxy)cinnamic monoterpenyl esters in biomass solvent: Mechanism underlying different reaction efficiency

(Hydroxy)cinnamic acids (HCAs), a kind of prevalent phenolic acid compound, boast diverse biological activities. However, their limited liposolubility impedes their utilization in oil-based systems. Addressing this challenge, we presented an eco-friendly approach to synthesize (hydroxy)cinnamic monoterpenyl esters in biomass solvent 2-methyltetrahydrofuran (2-MeTHF), grafting antibacterially active monoterpenyl onto phenolic acid compounds through esterification/transesterification. This green enzymatic catalytic strategy successfully synthesized a series of cinnamic monoterpenyl esters (yield >87.84%), p-coumaric monoterpenyl esters (yield >67.26%), and caffeic monoterpenyl esters (yield >10.55%). The mechanism difference in reaction efficiency of different hydroxyl cinnamic acids was revealed through kinetic calculation and molecular docking. As the number of hydroxyl group increased, the affinity between substrates and lipase decreased, which was reflected by the Km value, in which the Km value of cinnamic acid, p-coumaric acid and caffeic acid were 23.72, 52.04 and 60.05, respectively. Furthermore, molecular docking results showed that the strong binding of the hydroxyl groups to the hydrophobic cavity of the lipase resulted in the need for more energy to twist the reaction site closer to the active center during the reaction. This research provided a green and feasible route for the synthesis of phenolic acid ester derivatives.

Superoxide Ion-Assisted Radical Cascade Reaction: Synthesis of 3-nitro-4-aryl-2H-chromen-2-ones from Aryl Alkynoate Esters under Methylene Blue Visible Light Photocatalysis

Background: From an industries and academic perspective, there is a need for a method for producing 3-nitro-4-aryl-2H-chromen-2-ones from aryl alkynoate esters that is both economic and environmental benign. In this context, superoxide ion-assisted radical cascade reaction can be an efficient and greener protocol. Objective: Herein, we have demonstrated an unprecedented methylene blue (MB) visible light photocatalysis for the production of a series of 3-nitro-4-aryl-2H-chromen-2-ones from readily available aryl alkynoate esters and a nitrating agent in solution. Methods: Synthesis of 3-nitro-4-aryl-2H-chromen-2-ones has been performed in the presence of aryl alkynoate ester, TBAN, DIPEA, solvent, catalyst and molecular oxygen under visible light irradiation at room temperature. The products were purified by column chromatography using silica gel, and the mixture of ethyl acetate/petroleum ether as an eluting solvent and characterized by IR, NMR and mass spectroscopic analysis. Results: A series of aryl alkynoate esters were successfully nitrated into corresponding 3-nitro-4- aryl-2H-chromen-2-ones with good isolated yields by this protocol, in which the key NO2-radicals formed by the action of superoxide ion (O2−·). Conclusion: In contrast to the literature-reported methods of synthesis of 3-nitro-4-aryl-2Hchromen- 2-ones, the process described here for making 3-nitro-4-aryl-2H-chromen-2-ones uses methylene blue visible light photocatalysis, is inexpensive, mild, does not require a metal precursor or high temperatures, and is successful when using the direct sunlight.

Nature-Inspired Radical Pyridoxal-Mediated C-C Bond Formation.

Pyridoxal-5'-phosphate (PLP) and derivatives of this cofactor enable a plethora of reactions in both enzyme-mediated and free-in-solution transformations. With few exceptions in each category, such chemistry has predominantly involved two-electron processes. This sometimes poses a significant challenge for using PLP to build tetrasubstituted carbon centers, especially when the reaction is reversible. The ability to access radical pathways is paramount to broadening the scope of reactions catalyzed by this coenzyme. In this study, we demonstrate the ability to access a radical PLP-based intermediate and engage this radical intermediate in a number of C-C bond-forming reactions. By selection of an appropriate oxidant, single-electron oxidation of the quinonoid intermediate can be achieved, which can subsequently be applied to C-C bond-forming reactions. Through this radical reaction pathway, we synthesized a series of α-tertiary amino acids and esters to investigate the substrate scope and identify nonproductive reaction pathways. Beyond the amino acid model system, we demonstrate that other classes of amine substrates can be applied in this reaction and that a range of small molecule reagents can serve as coupling partners to the semiquinone radical. We anticipate that this versatile semiquinone radical species will be central to the development of a range of novel reactions.

Photoinduced Phase Transitions of Imine-Based Liquid Crystal Dimers with Twist-Bend Nematic Phases.

Photoisomerizable molecules in liquid crystals (LCs) allow for photoinduced phase transitions, facilitating applications in a wide variety of photoresponsive materials. In contrast to the widely investigated azobenzene structure, research on the photoinduced phase-transition behavior of imine-based LCs is considerably limited. We herein report the thermal and photoinduced phase-transition behaviors of photoisomerizable imine-based LC dimers with twist-bend nematic (NTB) phases. We synthesize two homologous series of ester- and thioether-linked N-(4-cyanobenzylidene)aniline-based bent-shaped LC dimers with an even number of carbon atoms (n = 2, 4, 6, 8, and 10) in the central alkylene spacers, namely, CBCOOnSBA(CN) and CBOCOnSBA(CN), possessing oppositely directed ester linkages, C=OO and OC=O, respectively. Their thermal phase-transition behavior is examined using polarizing optical microscopy and differential scanning calorimetry. All dimers form a monotropic NTB phase below the temperature of the conventional nematic (N) phase upon cooling. Remarkably, the NTB phases of CBCOOnSBA(CN) (n = 2, 4, 6, and 8) and CBOCOnSBA(CN) (n = 6 and 8) supercool to room temperature and vitrify without crystallization. In addition, the phase-transition temperatures and entropy changes of CBCOOnSBA(CN) are lower than those of CBOCOnSBA(CN) at the same n. Under UV light irradiation, the NTB and N phases transition to the N and isotropic phases, respectively, and reversibly return to their initial LC phases when the UV light is turned off.

Prolonged corrosion protection via application of 4-ferrocenylbutyl saturated carboxylate ester derivatives with superior inhibition performance for mild steel

A series of 4-ferrcenylbutyl carboxylate esters with different alkyl chain length (C2-C4) of carboxylic acids were synthesized using Fe3O4@SiO2@(CH2)3-Im-bisEthylFc[I] nanoparticles as catalyst and have been characterized with FT-IR, 1H NMR, and 13C NMR. Ferrocenyl-based esters were used as corrosion inhibitors of mild steel in the 1M HCl solution as corrosive media. The corrosion inhibition efficiency of the synthesized ferrocenyl-based esters has been assessed by electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), atomic force microscopy (AFM), and scanning electron microscopy (SEM). The 4-ferrocenylbutyl propionate showed a more effective corrosion inhibition behavior among the studied esters with 96% efficiency after immersion in the corrosive media for 2 weeks. The corrosion inhibition mechanism is dominated by formation of passive layer of inhibitor on the surface of the mild steel by adsorption. Moreover, the adsorption characteristics of 4-butylferrcenyl carboxylate esters on mild steel were thoroughly explored using density functional theory calculations. It was found that the Fe atoms located around the C impurity in the mild steel are the most efficient and active sites to adsorb 4-butylferrcenyl carboxylate esters.

Enzymatic Synthesis of Austroeupatol Esters with Enhanced Antiprotozoal Activity.

Austroeupatol, the principal diterpene isolated from the invasive shrub Austroeupatorium inulifolium, holds promise for structural diversification and biological assessment of its derivatives due to its abundant availability and high yield isolation. We propose an efficient enzymatic synthesis of a series of austroeupatol esters derived from aliphatic and heterocyclic carboxylic acids. Systematic optimization of reaction parameters, including enzyme type and quantity, acylating agent amount, solvent, and temperature, was conducted. Thermomyces lanuginosus lipase in cyclohexane at 55 °C, yielded esters with favorable conversion rates. Through enzymatic catalysis, mono- and diacylated derivatives were obtained, with a diacylation-monoacylation ratio influenced by temperature and acylating agent amount. The antiprotozoal activity of austroeupatol and all synthesized derivatives was evaluated, observing that acylation improved it. The 19-valeroyl, 19-indolylpropyl, and 19-octyl derivatives were the most potent compounds against Trypanosoma cruzi and Leishmania infantum, highlighting this approach as a valuable method for synthesizing austroeupatol derivatives as potential antiparasitic agents.

Sugar-Based Surfactants: Effects of Structural Features on the Physicochemical Properties of Sugar Esters and Their Comparison to Commercial Octyl Glycosides.

Two series of sugar esters with alkyl chain lengths varying from 5 to 12 carbon atoms, and with a head group consisting of glucose or galactose moieties, were synthesized. Equilibrium surface tension isotherms were measured, yielding critical micellar concentration (CMC) surface tensions at CMC (γcmc) and minimum areas at the air-water interface (Amin). In addition, Krafft temperatures (Tks) were measured to characterize the ability of molecules to dissolve in water, which is essential in numerous applications. As a comparison to widely used commercial sugar-based surfactants, those measurements were also carried out for four octyl d-glycosides. Impacts of the linkages between polar and lipophilic moieties, alkyl chain lengths, and the nature of the sugar head group on the measured properties were highlighted. Higher Tk and, thus, lower dissolution ability, were found for methyl 6-O-acyl-d-glucopyranosides. CMC and γcmc decreased with the alkyl chain lengths in both cases, but Amin did not appear to be influenced. Both γcmc and Amin appeared independent of the ester group orientation. Notably, alkyl (methyl α-d-glucopyranosid)uronates were found to result in noticeably lower CMC, possibly due to a closer distance between the carbonyl function and the head group.

Hydrodeoxygenation of biomass-derived fatty acids and esters to biofuels on RuRe/ZSM-5 catalysts: Synergistic effects of ReOx and Brønsted acid sites

The hydrodeoxygenation of fatty acids and esters is a critical pathway to produce biofuels. We report an efficient RuRe/ZSM-5(18) catalyst for hydrodeoxygenation of methyl laurate, the selectivity of n-C12H26 reached up to 95.2 % at complete conversion under the reaction conditions of 200 °C, 3 MPa H2, 3 h. The contribution of ReOx and acid sites was discussed from the perspective of dynamics and thermodynamics. ReOx was available for the adsorption of substrate and intermediates, the acidity from ReOx species and ZSM-5 are conducive to the cleavage of CO bond. The synergistic effects of ReOx and Brønsted acid sites induced Ru0 species to be electron-deficient, which preferred to adsorb aldehyde group in a linear adsorption configuration and facilitated for the hydrogenation of the aldehyde intermediate to alcohol, followed by dehydration to produce hydrocarbons. Thus, RuRe/ZSM-5(18) catalyst presented superior activity and chemoselectivity in the hydrodeoxygenation of methyl laurate as well as a series of fatty acids and esters without loss in carbon numbers in reactant.

A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies

A variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 enzyme at 5 μM via ELISA experiment. Compound L-37 (1 μM) also inhibited the PGF1 production as well as the expression of COX-1, but displayed weak inhibition activity towards the Leukotrienes (LT) and Thromboxane-B2 (TXB-2) production. However, the expression of 5-LOX was significantly inhibited by compound L-39 at 5 μM. Xylene-induced ear edema model was explored for in-vivo anti-inflammatory evaluation, compound L-37 showed similar inhibitory activity compared with celecoxib, approximately 80% at 50 mg/kg dosage. Every outcome showed that the newly synthesized compounds can effectively inhibit inflammation.

Synthesis and Characterization of Metronidazole and Heterocycle Ester Dyads for Tyrosinase Inhibitory Activity

Tyrosinase is an important copper-based enzyme mainly involved in skin pigmentation. The inhibition of the tyrosinase enzyme attracts importance in cosmetic and medicinal chemistry industry for its applications in skin whitening and anti-browning agents for humans as well as in food, agriculture industries. Imidazole based Metronidazole and its derivatives are widely accepted drug for wide range of diseases. Therefore, the present report involves the synthesis of heterocyclic derivatives of metronidazole and investigation of its efficacy towards the tyrosinase inhibitory activity. A series of metronidazole esters were synthesized and their chemical structures were confirmed using spectral techniques like, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and liquid chromatography-mass spectrometry (LC-MS). All the compounds were evaluated for its tyrosinase inhibitory activity by oxidation of 3,4-dihydroxyphenylalanine in the presence of the synthesized esters(I-VIII) with kojic acid as standard. Among the synthesized compounds, VII (isonicotinic ester) and VIII (quinoline ester) demonstrated significant activity IC50 values 92.5 and 91.8µM respectively. Further molecular docking experiments were carried out for the synthesized compounds with 2y9w protein exhibited greater number of physical interactions for compounds VII and VIII than the other compounds in the series confirming the mushroom tyrosinase activity.

Discovery of a series of portimine-A fatty acid esters in mussels

Vulcanodinium rugosum is a benthic dinoflagellate known for producing pinnatoxins, pteriatoxins, portimines and kabirimine. In this study, we aimed to identify unknown analogs of these emerging toxins in mussels collected in the Ingril lagoon, France. First, untargeted data acquisitions were conducted by means of liquid chromatography coupled to hybrid quadrupole-orbitrap mass spectrometry. Data processing involved a molecular networking approach, and a workflow dedicated to the identification of biotransformed metabolites. Additionally, targeted analyses by liquid chromatography coupled to triple quadrupole mass spectrometry were also implemented to further investigate and confirm the identification of new compounds. For the first time, a series of 13-O-acyl esters of portimine-A (n = 13) were identified, with fatty acid chains ranging between C12:0 and C22:6. The profile was dominated by the palmitic acid conjugation. This discovery was supported by fractionation experiments combined with the implementation of a hydrolysis reaction, providing further evidence of the metabolite identities. Furthermore, several analogs were semi-synthesized, definitively confirming the discovery of these metabolization products. A new analog of pinnatoxin, with a molecular formula of C42H65NO9, was also identified across the year 2018, with the highest concentration observed in August (4.5 μg/kg). The MS/MS data collected for this compound exhibited strong structural similarities with PnTX-A and PnTX-G, likely indicating a substituent C2H5O2 in the side chain at C33. The discovery of these new analogs will contribute to deeper knowledge of the chemodiversity of toxins produced by V. rugosum or resulting from shellfish metabolism, thereby improving our ability to characterize the risks associated with these emerging toxins.

Radioprotective effectiveness of a novel delta-tocotrienol prodrug on mouse hematopoietic system against 60Co gamma-ray irradiation through inducing granulocyte-colony stimulating factor production

Considering the increasing risk of nuclear attacks worldwide, the development of develop potent and safe radioprotective agents for nuclear emergencies is urgently needed. γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have demonstrated a potent radioprotective effect by inducing the production of granulocyte-colony stimulating factor (G-CSF) in vivo. However, their application is limited because of their low bioavailability. The utilization of ester prodrugs can be an effective strategy for modifying the pharmacokinetic properties of drug molecules. In this study, we initially confirmed that DT3 exhibited the most significant potential for inducing G-CSF effects among eight natural vitamin E homologs. Consequently, we designed and synthesized a series of DT3 ester and ether derivatives, leading to improved radioprotective effects. The metabolic study conducted in vitro and in vivo has identified DT3 succinate 5b as a prodrug of DT3 with an approximately seven-fold higher bioavailability compared to DT3 alone. And DT3 ether derivative 8a were relatively stable and approximately 4 times more bioavailable than DT3 prototype. Furthermore, 5b exhibited superior ability to mitigate radiation-induced pancytopenia, enhance the recovery of bone marrow hematopoietic stem and progenitor cells, and promote splenic extramedullary hematopoiesis in sublethal irradiated mice. Similarly, 8a shown potential radiation protection, but its radiation protection is less than DT3. Based on these findings, we identified 5b as a DT3 prodrug, and providing an attractive candidate for further drug development.

Niosomal Bupropion: Exploring Therapeutic Frontiers through Behavioral Profiling.

Bupropion (Bup) belongs to the norepinephrine-dopamine reuptake inhibitor (NDRI) class and it is the only FDA-approved drug of its class for the treatment of major depressive disorder (MDD), sold under the name of Wellbutrin. Although bupropion is effective in suppressing the symptoms, its regular use and overdose might lead to seizures and liver failure. Thus, we aimed to nanoformulate bupropion onto a niosomal vesicle to improve its efficacy and achieve the same therapeutic effect at lower scheduled doses. A thin film hydration method was adopted to synthesize and optimize Bup entrapped niosomes using three different surfactants of the sorbitan ester series (Span 20, 40, and 60) in combination with cholesterol. The optimization data determined that the niosome formulated with a cholesterol-to-surfactant ratio of 1:1.5 is the most stable system, with the Bup entrapped niosomes containing Span 20 (Bup@N20C) exhibiting minimal in vitro and in vivo toxicity, and demonstrating the sustained release of Bup in artificial cerebrospinal fluid (ACSF). The Bup@N20C formulation showed increased exploration activity and reduced irregular movements in reserpine-induced depression in the adult zebrafish model, suggesting the potential for mood improvement through the suppression of depression-like behavior which was established by statistical analysis and trajectory data. The Bup@N20C-treated group even surpasses the treatment effect of the positive control group and is comparable to the control group. Hence, it can be inferred that niosomal formulations of Bup represent a promising delivery system capable of achieving the brain delivery of the cargo by bypassing the blood-brain barrier facilitated by their small architectural structure.