Design,synthesis, and evaluation of novel l-phenylglycine derivatives as potential PPARγ lead compounds

In accordance with the structural characteristics of thiazolidinedione drugs and highly bioactive tyrosine derivatives, we tentatively designed the l-phenylglycine derivatives TM1 and TM2 based on basic principles of drug design and then synthesized them. The in vitro screening of peroxisome proliferator-activated receptor gamma (PPARγ) activated activity, α-glucosidase inhibitory and dipeptidyl peptidase-4 inhibitory activities showed that the novel molecule M5 had efficient PPAR response element (PPRE) activated activity (PPRE relative activity 105.04% at 10?μg·mL^?1 compared with the positive control pioglitazone, with 100% activity). Therefore, M5 was selected as the hit compound from which the TM3 and TM4 series of compounds were further designed and synthesized. Based on the PPRE relative activities of TM3 and TM4, we discovered another new molecule, TM4h, which had the strongest PPRE relative activity (120.42% at 10?μg·mL^?1). In addition, the concentration-dependent activity of the highly active compounds was determined by assaying their half-maximal effective concentration (EC₅₀) values. The molecular physical parameter calculation and the molecular toxicity prediction were used to theoretically evaluate the lead-likeness and safety of the active compounds. In conclusion, we identified a potential PPARγ lead molecule and developed a tangible strategy for antidiabetic drug development.     

Synthesis,insecticidal evaluation and mode of action of novel anthranilic diamide derivatives containing sulfur moiety as potential ryanodine receptor activators

Anthranilic diamide insecticide could control lepidopteran pests by selectively binding and activating insect ryanodine receptors (RyRs), and the unique mode of action is different from other conventional insecticides. In order to discover new anthranilic diamide insecticide as ryanodine receptors activators, a series of 11 novel anthranilic diamides derivatives (Ia-k) were synthesized and confirmed by melting point, ¹H NMR, ¹³C NMR and elemental analyses. The preliminary bioactivity revealed that most title compounds showed moderate to remarkable activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Especially, compounds Ia and If, which exhibited 100% larvicidal activity against oriental armyworm at 1.0?mg?L^?1, and comparable to that of chlorantraniliprole (100% at 1?mg?L^?1). If displayed 60% insecticidal activity against diamondback moth at 0.01?mg?L^?1, better than chlorantraniliprole (45% at 0.01?mg?L^?1). The preliminary structure activity relationships were discussed. In addition, the calcium imaging experiment indicated that the insect ryanodine receptor is the potential target of If.     

Synthesis and bioactivities evaluation of l-pyroglutamic acid analogues from natural product lead

A series of l-pyroglutamic acid analogues from natural product lead were designed and synthesized, as well as their antifungal activities against Phytophthora infestans, neuritogenic activities, antibacterial activities and anti-inflammatory activities are described. The bioassays and SAR study showed that the majority of l-pyroglutamic acid esters have a significant antifungal activity against P. infestans, especially 2d and 2j demonstrated the best activities with EC₅₀ values of 1.44 and 1.21?μg?mL^?1, which were about seven times that of commercial azoxystrobin (7.85?μg?mL^?1). Moreover, compounds 2e, 2g and 4d displayed anti-inflammatory activity against LPS-induced NO production in BV-2 microglial cells; neuritogenic activity in NGF-induced PC-12 cells is the same activity. This study demonstrates that compounds 2d and 2j are potential drugs to control P. infestans.     

Anthranilic diamides derivatives as potential ryanodine receptor modulators: Synthesis,biological evaluation and structure activity relationship

A series of novel anthranilic diamides derivatives (7a–s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, ¹H NMR, ¹³C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Above all, the larvicidal activity of 7o against oriental armyworm was 100% and 40% at 0.25 and 0.1?mg?L^?1, comparable to that of the standard chlorantraniliprole (100%, 0.25?mg?L^?1 and 20%, 0.1?mg?L^?1). What is more, 7o against diamondback moth displayed 90% insecticidal activity at 0.01?mg?L^?1, superior to chlorantraniliprole (45%, 0.01?mg?L^?1). The experiments 7o on the American cockroach (Periplaneta Americana) heart beating rates (Dorsal vessel) and contractile force were compared with chlorantraniliprole. In addition, 7o could affect the calcium homeostasis in the central neurons of the third larvae of oriental armyworm, which revealed that the ryanodine receptor is the potential target of 7o. The density functional theory (DFT) calculation results revealed the amide bridge, the benzene ring of anthraniloyl moiety and pyrazole ring might play an important role in the insecticidal activity through hydrophobic interactions and π-π conjugations.     

Design,synthesis, insecticidal activity and molecular docking of doramectin derivatives

A series of new doramectin derivatives containing carbamate, ester and sulfonate were synthesized, and their structures were characterized by ¹H and ¹³C nuclear magnetic resonance (NMR) and high-resolution mass spectrum (HRMS). Their insecticidal activities against oriental armyworm, diamondback moth, and corn borer were evaluated and compared with the parent doramectin and commercial avermectins, metolcarb, fenpropathrin. Among all compounds, three compounds (3a, 3g and 3h) showed excellent insecticidal effect. In particular, compound 3g containing cyclopropyl carbamate against oriental armyworm, diamondback moth, and corn borer, exhibited the most promising insecticidal activity with the final mortality rate of 66.67%, 36.67%, 40.00% at the concentration of 12.5 mg/L, respectively. The LC₅₀ values of 3g were 5.8859, 22.3214, and 22.0205 mg/L, showing 6.74, 2.23, 2.21-fold higher potency than parent doramectin (LC₅₀ values of 39.6907, 49.7736, and 48.6129 mg/L) and 6.83, 1.93, 3.36-fold higher potency than commercial avermectins (LC₅₀ values of 40.2489, 42.9922, and 73.9508 mg/L). Additionally, molecular docking simulations revealed that 3g displayed stronger hydrogen-bonding action in binding with the GABA receptor than parent doramectin, which were crucial for keeping high insecticidal activity. The present work demonstrated that these compounds containing alkyl carbamate group could be considered as potential candidates for the development of novel pesticides in the future.     

Optimization of culture conditions and bench-scale production of anticancer enzyme L-asparaginase by submerged fermentation from Aspergillus terreus CCT 7693

L-Asparaginase amidohydrolase (EC 3.5.1.1) has received significant attention owing to its clinical use in acute lymphoblastic leukemia treatment and non-clinical applications in the food industry to reduce acrylamide (toxic compound) formation during the frying of starchy foods. In this study, a sequential optimization strategy was used to determine the best culture conditions for L-asparaginase production from filamentous fungus Aspergillus terreus CCT 7693 by submerged fermentation. The cultural conditions were studied using a 3-level, central composite design of response surface methodology, and biomass and enzyme production were optimized separately. The highest amount of biomass (22.0?g·L^?1) was obtained with modified Czapek–Dox medium containing glucose (14?g·L^?1), L-proline (10?g·L^?1), and ammonium nitrate (2?g·L^?1) fermented at 37.2?°C and pH 8.56; for maximum enzyme production (13.50?U·g^?1), the best condition was modified Czapek–Dox medium containing glucose (2?g·L^?1), L-proline (10?g·L^?1), and inoculum concentration of 4.8?×?10⁸ espore·mL^?1 adjusted to pH 9.49 at 34.6?°C. The L-asparaginase production profile was studied in a 7?L bench-scale bioreactor and a final specific activity of 13.81?U·g^?1 was achieved, which represents an increase of 200% in relation to the initial non-optimized conditions.     

Synthesis,biological activities and SAR studies of new 3-substitutedphenyl-4-substitutedbenzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors

A series of new 3-substitutedphenyl-4-substitutedbenzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases were synthesized through Mannich reaction with high yields. Their structures were confirmed by means of IR, ¹H NMR, ¹³C NMR and elemental analysis. The preliminary bioassay indicated that compounds 7g, 7h and 7l exhibited potent in vitro inhibitory activities against ketol-acid reductoisomerase (KARI) with K_i value of (0.38?±?0.25), (6.59?±?2.75) and (8.46?±?3.99)?μmol/L, respectively, and were comparable with IpOHA. They could be new KARI inhibitors for follow-up research. Some of the title compounds also exhibited obvious herbicidal activities against Echinochloa crusgalli and remarkable in vitro fungicidal activities against Physalospora piricola and Rhizoctonia cerealis. The SAR of the compounds were analyzed, in which the molecular docking revealed the binding mode of 7g with the KARI, and the 3D-QSAR results provided useful information for guiding further optimization of this kind of structures to discover new fungicidal agents towards Rhizoctonia cerealis.     

Thioether-bridged arylalkyl-linked N-phenylpyrazole derivatives: Design,synthesis, insecticidal activities,structure-activity relationship and molecular-modeling studies

Owing to thioether diverse physicochemical properties by non-covalent interactions with bio-macromolecules, thioether derivatives containing heterocyclic moiety are known for their interesting insecticidal bioactivities and attracting considerable attention as neuroactive insecticides. Here we synthesis a series of novel thioether bridged N-phenylpyrazole derivatives incorporating various (hetero)aromatic substituents into 4-position of the pyrazole ring. Structure-activity relationship (SAR) studies resulted in compounds 6d and 7d with the most potent insecticidal activity among the series containing various substituted benzene substituents (LC₅₀?=?13.70–25.47?μg/g). Further optimization to increase the lipophilicity and charge density of aromatic substituents of compounds 6d and 7d resulted in compounds 12d, 14d and 16d with sulfur-containing heterocycle substituents possessing good insecticidal activity against Musca domestica L. among the series (LC₅₀?=?0.67–1.30?μg/g). The thioether bridge N-phenylpyrazole derivatives, which exhibit different length of the spacer arm introduced between N-phenylpyrazole moiety and the (hetero)aromatic substituents, were also prepared and evaluated. By contrast, the insecticidal activities of compounds containing the short thioether bridge, 1,2-bis((hetero)aromatic thio) ethane, are higher than that containing the long thioether bridge, 1,3-bis((hetero)aromatic thio) propane. The results of molecular docking and pharmacophore analyses indicated A299, T303, and L306 of a subunit were essential to form non-covalent interactions contacts with the ligands. Specially, the sulfur-containing heterocycle substituent derivatives 12d and 14d as the sterically favored areas could form the important hydrophobic interactions with the deeper residue P295.     

Caloric content of plant species and its role in a Leymus chinensis steppe community of Inner Mongolia, China

The caloric contents of 42 species and their composition in a Leymus chinensis steppe community of Inner Mongolia, China were determined and analyzed based on the field experiment for 11 years. The caloric content (x ± SD) of aboveground parts of plant species varied from (13156 ± 1141) J·g^?1 (ash contained) to (18141 ± 527) J·g^?1. The average caloric content of all species was (16899 ± 840) J·g^?1 and the inter-specific CV (coefficient of variation) was 4.9%. Of all the species, Caragana microphylla had the highest caloric content (18142 J·g^?1). Grasses had a higher average caloric content ((17425 ± 291) J·g^?1) than forbs ((16734 ± 844)J·g^?1). When the herbaceous species were classified into subgroups according to life-form and growth-form, the order of average caloric contents, from high to low, was: tall grasses ((17717 ± 92) J·g^?1) > legume ((17228 ± 433) J·g^?1) > short grasses ((17250 ± 218) J·g^?1) > remaining forbs ((16784 ± 529) J·g^?1) > subshrubs ((16719 ± 69) J·g^?1) > annuals and biennials ((15911 ± 1759) J·g^?1). There was a positive correlation (P < 0.05) between the caloric contents of 42 species and their relative biomass in the community. When all species were classified into 3 groups according to their composition in the community, the average caloric contents, weighed by the species relative biomass, followed the order: dominant (17740 J·g^?1) > companion (17244 J·g^?1) > incidental (16653 J·g^?1). The plants with high caloric contents were more competitive, which allowed them to gain a dominant status, whereas the competitive abilities of plants with low caloric contents were generally weak. The latter made up the companion or incidental species in a steppe community.     

Design,Synthesis, Insecticidal Activities and Molecular Docking of Sulfonamide Derivatives Containing Propargyloxy or Pyridine Groups

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC₅₀) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC₅₀=18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.     

Macrocystis angustifolia is a potential source of enzyme inhibitors linked to type 2 diabetes and dementia

In continuation of the screening of South African seaweeds to identify potential candidates for the development of pharmaceutically active functional foods, we investigated the inhibitory effects of a crude 80 % methanol extract, solvent fractions and isolated compounds from the kelp Macrocystis angustifolia against enzymes involved in type 2 diabetes and dementia. Repeated column fractionation of the ethyl acetate fraction of the crude extract of M. angustifolia afforded two phenol derivatives identified by spectroscopic analyses (1D and 2D NMR): 4-(2-hydroxyethyl)phenol (tyrosol) (1) and 4-(1,2-dihydroxyethyl)phenol (2). These compounds were isolated from a marine alga for the first time. The ethyl acetate (IC₅₀?=?14.08?±?1.21 μg mL^?1) and butanol (IC₅₀?=?77.94?±?11.69 μg mL^?1) fractions exhibited potent inhibition against α-glucosidase and acetylcholinesterase (AChE) enzymes, respectively. Tyrosol (1) and its derivative, 4-(1,2-dihydroxyethyl)phenol (2), showed potent inhibition against both α-glucosidase and AChE enzymes. Based on in silico evaluation, these two compounds are anticipated to possess sufficient oral bioavailability in accordance to the Lipinski Rule of Five without any toxicity risk. Natural α-glucosidase and AChE inhibitors from M. angustifolia offer a novel approach to control type 2 diabetes and dementia.     

Polyprenylated polycyclic acylphloroglucinol: Angiogenesis inhibitor from Garcinia multiflora

A new polyprenylated polycyclic acylphloroglucinol, garcimultiflorone K (1), has been isolated from the stems of Garcinia multiflora, together with two known compounds, garcimultiflorone A (2) and garcimultiflorone B (3). The structure of new compound 1 was determined through spectroscopic methods including 1D and 2D NMR and MS analyses. The anti-angiogenic and anti-cancer effects of compounds 1–3 were evaluated in human endothelial progenitor cells (EPCs) and cancer cells. Of these, garcimultiflorone K (1) displayed the most potent anti-angiogenic property by suppressing cell growth and tube formation of EPCs. Compound 1 also exhibited growth-inhibitory activities against human hepatocellular carcinoma cell line SK-Hep-1 and hormone refractory prostate cancer cell line PC-3 with GI₅₀ values of 4.3?±?1.6 and 6.6?±?0.4?μM, respectively.     

Synthesis,X-ray crystal structure study and antitumoral evaluations of 5,6-disubstituted pyrimidine derivatives

5,6-Disubstituted pyrimidine derivatives (3–20) were prepared by intramolecular cyclization reaction of α-(1-carbamyliminomethylene)-γ-butyrolactone (2) with sodium ethoxide and subsequent chemical transformation of 2-hydroxy group in C-5 side chain as well as lithiation reaction for introduction of acyclic side chain at C-6. All compounds were characterized by ¹H NMR, ¹³C NMR and mass spectra. Structures of compounds 4, 7 and 14 were unambiguously confirmed by X-ray crystal structural analysis. Supramolecular structures of these three compounds differ significantly. Two N–H?O and one C–H?O hydrogen bonds in 4 form three-dimensional network. One O–H?N hydrogen bond and one π?π interaction self-assemble the molecules of 7 into sheets. In supramolecular aggregation of 14, only π?π stacking interactions participate, so forming chains. The compounds were evaluated for their cytostatic activities against human malignant cell lines. Of all tested compounds, 2,4-dimethoxy-5-methoxytritylethylpyrimidine (9) and 2,4-dichloro-5-chloroethylpyrimidine (14) exhibited the most prominent inhibitory effects. Furthermore, compound 14 showed marked activity against human colon carcinoma (IC₅₀ = 0.4 μM).     

Ventilation and oxygen consumption in the hagfish, Myxine glutinosa L.

Ventilation was measured directly in the hagfish, Myxine glutinosa L., by means of an electro-magnetic blood flowmeter. Ventilatory flow and frequency increased from 0.86 ± 0.27 ml·min^?, and 18.2 ± 5.1·min^?, respectively, at 7°C to 1.70 ± 0.20 ml·min^?, and 70.1 ± 9.5·min^? at 15 ·C.Standard oxygen consumption,V?O₂, was measured in non-buried hagfish. V?O₂ was 0.57 ± 0.17μl O₂·g^?1·min^?1 at 7°C, and 0.85 ± 0.12μl O₂·g^?1·min^?1 at 15°C.     

Design,synthesis and insecticidal evaluation of aryloxy dihalopropene derivatives

Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical structures were confirmed by ¹H NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity against P. xylostella at 6.25 mg/L, while pyridalyl showed 50% insecticidal activity at the same concentration. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control of P. xylostella at 75–150 g a.i./ha, and the mortality of P. xylostella for treatment with compound 10e at 75 g a.i./ha was equivalent to pyridalyl at 105 g a.i./ha.     

Synthesis and anti-HSV activity of tricyclic penciclovir and hydroxybutylguanine derivatives

A series of tricyclic penciclovir (PCV) and hydroxybutylguanine (HBG) derivatives have been prepared with enhanced lipophilicity following an efficient synthetic route. All the novel tricyclic derivatives were evaluated for inhibitory activity against herpes simplex virus 1 and 2 (HSV-1, HSV-2) and thymidine kinase deficient (ACV resistant) HSV-1. The tricyclic HBG derivatives were devoid of inhibitory activity however several of the tricyclic PCV derivatives showed promising antiviral activity, in particular 9g (R?=?4-MeO-C₆H₄) displayed good inhibitory activity (HSV-1 EC₅₀ 1.5?μM, HSV-2 EC₅₀ 0.8?μM) and retained inhibitory activity in HSV-1 TK^? cells (EC₅₀ 0.8?μM). Computational docking experiments supported the biological data observed and this preliminary study provides useful data for further development of tricyclic acyclic nucleoside derivatives with improved lipophilicity and retention of activity in HSV-1 TK deficient strains. Also, the new tricyclic derivatives were evaluated against a broad range of other DNA and RNA viruses, but were found to be inactive at subtoxic concentrations. In addition, weak to moderate cytostatic effect was observed for the new compounds.     

In silico, NMR and pharmacological evaluation of an hydroxyoxindole cholinesterase inhibitor

From a screening study of various potential inhibitors for cholinesterases (ChEs), compound (rac)-1 (4-((3-hydroxy-2-oxo-3-phenylindolin-1-yl) methyl) piperidin-1-ium chloride) showed an IC₅₀ of 18?μM for butyrylcholinesterase (BuChE). Herein we present a toxicological and pharmacological evaluation of (rac)-1 to determine its potential for use as an alternative ChE inhibitor for the treatment of Alzheimer’s disease. The strategy adopted included in vivo and ex vivo studies with mouse models, Molecular Modelling and Saturation Transfer Difference (STD) NMR studies.Preliminary molecular docking studies were conducted with both (R) and (S)-1 with acetylcholinesterase (AChE) and BuChE, prior to advancing to the mouse model, and indeed favorable interactions were observed, with (R)-1 showing the best binding with AChE and (S)-1 with BuChE. STD-NMR studies were used to successfully validate these results. Toxicological studies were also conducted using the Artemia salina model, with donepezil as reference. It was found that in the in vivo mouse studies that (rac)-1 presented a slightly better inhibition of AChE (0.096?µmol.min^?1.mg^?1) than donepezil (0.112?µmol.min^?1.mg^?1) and the same level of inhibition for BuChE as donepezil (0.014?µmol.min^?1.mg^?1).     

Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase,monoamine oxidases and β-amyloid aggregation inhibitory activities as potential agents against Alzheimer’s disease

A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC₅₀?=?0.29?±?0.01?μM and 0.46?±?0.02?μM, respectively), MAO-A (IC₅₀?=?8.2?±?0.08?μM and 7.9?±?0.07?μM, respectively) and MAO-B (IC₅₀?=?20.1?±?0.16?μM and 43.8?±?2.0% at 10?μM, respectively) inhibitory activities, moderate self-induced Aβ_1–42 aggregation inhibitory potency (35.4?±?0.42% and 48.0?±?1.53% at 25?μM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD.     

Uptake of glycine and release of primary amines by the polychaete Nereis virens (Sars) and the mud snail Hydrobia neglecta muus

Uptake of glycine and release of primary amines by the polychaete Nereis virens (Sars) and the mud snail Hydrobia neglecta Muus was investigated. In a flow system, Nereis virens had a net influx of glycine of 32 to 39 nmol·g^?1 fresh wt·h from a 5-μM solution of glycine. Simultaneously, an efflux of primary amines of 14 nmol·g^?1·h^?1 was measured. The experiments indicated that glycine uptake and release of primary amines are two independent processes. Glycine was absorved by Hydrobia neglecta from 50-μM solutions at an influx of 175 nmol·g^?1 organic wt·h^?1, and simultaneously, there was an independent efflux of 25 nmol primary amine·g^?1·h^?1. In the experiments, released primary amines from both species increased the ambient concentration of primary amines, but after various periods of time these concentrations apparently stabilized. Finally, the significance of micro-organisms in amino-acid uptake experiments is considered.     

Anti-neuroinflammatory effects of sesquiterpenoids isolated from Nardostachys jatamansi

Two new nardosinone-type sesquiterpenoids, namely kanshone J (1) and kanshone K (2) along with seven known terpenoids (3–9) were isolated from the rhizomes and roots of Nardostachys jatamansi DC (Valerianaceae). The structures of these compounds were determined mainly by analysis of 1D-, 2D-NMR and MS data. In addition, the absolute configuration of compound 1 was assigned by application of the modified Mosher’s method. In an initial assay to evaluate their anti-neuroinflammatory effects, compounds 1–5 and 9 exhibited dose-dependent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 cells, with IC₅₀ values ranging from 2.43 to 46.54?μM. Particularly, desoxo-narchinol A (3) and narchinol B (4) significantly inhibited LPS-induced NO overproduction in BV2 cells with IC₅₀ values of 3.48?±?0.47 and 2.43?±?0.23?μM, respectively. Furthermore, compounds 3 and 4 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E₂ (PGE₂), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF)-α, in LPS-stimulated BV2 and primary microglial cells.