In vitro inhibition of α-Synuclein aggregation and disaggregation of preformed fibers by polyphenol hybrids with 2-conjugated benzothiazole.

The misfolding and aggregation of α-Syn play a pivotal role in connecting diverse pathological pathways in Parkinson's disease (PD). Preserving α-Syn proteostasis and functionality by inhibiting its aggregation or disaggregating existing aggregates using suitable inhibitors represents a promising strategy for PD prevention and treatment. In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates and monomers. These findings offer valuable insights into the therapeutic potential of polyphenol hybrids with 2-conjugated benzothiazole targeting α-Syn aggregation in the treatment of PD.

The potential of Rhein's aromatic amines for Parkinson's disease prevention and treatment: α-Synuclein aggregation inhibition and disaggregation of preformed fibers.

The aggregation of α-Syn is a pivotal mechanism in Parkinson's disease (PD). Effectively maintaining α-Syn proteostasis involves both inhibiting its aggregation and promoting disaggregation. In this study, we developed a series of aromatic amide derivatives based on Rhein. Two of these compounds, 4,5-dihydroxy-N-(3-hydroxyphenyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (a5) and 4,5-dihydroxy-N-(2-hydroxy-4-chlorophenyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (a8), exhibited good binding affinities to α-Syn residues, demonstrating promising inhibitory activity against α-Syn aggregation in vitro, with low IC50 values (1.35 and 1.08 µM, respectivly). These inhibitors acted throughout the entire aggregation process by stabilizing α-Syn's conformation and preventing the formation of ß-sheet aggregates. They also effectively disassembled preformed α-Syn oligomers and fibrils. Preliminary mechanistic insights indicated that they bound to the specific domain within fibrils, inducing fibril instability, collapse, and the formation of smaller aggregates and monomeric α-Syn units. This research underscores the therapeutic potential of Rhein's aromatic amides in targeting α-Syn aggregation for PD treatment and suggests broader applications in managing and preventing neurodegenerative diseases.

Therapeutic potential of Coumarin-polyphenolic acid hybrids in PD: Inhibition of α-Syn aggregation and disaggregation of preformed fibrils, leading to reduced neuronal inclusion formation.

This study focuses on the discovery of new potential drugs for treating PD by targeting the aggregation of α-Syn. A series of hybrids combining Coumarin and phenolic acid were designed and synthesized. Four particularly promising compounds were identified, showing strong inhibitory effects with IC50 values ranging from low micromolar to submicromolar concentrations, as low as 0.63 µM. These compounds exhibited a higher binding affinity to α-Syn residues and effectively hindered the entire aggregation process, maintaining the proteostasis conformation of α-Syn and preventing the formation of ß-sheet aggregates. This approach holds significant promise for PD prevention. Additionally, these candidate compounds demonstrated the ability to break down preformed α-Syn oligomers and fibrils, resulting in the formation of smaller aggregates and monomers. Moreover, the candidate compounds showed impressive effectiveness in inhibiting α-Syn aggregation within nerve cells, thereby reducing the likelihood of α-Syn inclusion formation resembling Lewy bodies, which highlights their potential for treating PD.

Selective Photoelectrochemical Oxidation of Glycerol to Glyceric Acid on (002) Facets Exposed WO3 Nanosheets.

Glycerol is a byproduct of biodiesel production. Selective photoelectrochemical oxidation of glycerol to high value-added chemicals offers an economical and sustainable approach to transform renewable feedstock as well as store green energy at the same time. In this work, we synthesized monoclinic WO3 nanosheets with exposed (002) facets, which could selectively oxidize glycerol to glyceric acid (GLYA) with a photocurrent density of 1.7 mA cm-2 , a 73 % GLYA selectivity and a 39 % GLYA Faradaic efficiency at 0.9 V vs. reversible hydrogen electrode (RHE) under AM 1.5G illumination (100 mW cm-2 ). Compared to (200) facets exposed WO3 , a combination of experiments and theoretical calculations indicates that the superior performance of selective glycerol oxidation mainly originates from the better charge separation and prolonged carrier lifetime resulted from the plenty of surface trapping states, lower energy barrier of the glycerol-to-GLYA reaction pathway, more abundant active sites and stronger oxidative ability of photogenerated holes on the (002) facets exposed WO3 . Our findings show great potential to significantly contribute to the sustainable and environmentally friendly chemical processes via designing high performance photoelectrochemical cell via facet engineering for renewable feedstock transformation.

4-Arylidene curcumin derivatives in vitro inhibit α-Synuclein aggregation and disaggregate the preformed fibril.

This study focuses on the misfolding and aggregation of α-Syn as a central mechanism linking various pathological processes in PD. Maintaining α-Syn proteostasis through suitable inhibitors emerges as an effective approach to prevent PD. A more efficient strategy for PD treatment involves disintegrating neurotoxic oligomers and fibrils into normal functional α-Syn using inhibitors. To this end, a series of 4-arylidene curcumin derivatives were synthesized with a sheet-like conjugated skeleton and higher binding energies with α-Syn residues. Among these derivatives, three candidate compounds exhibited promising α-Syn aggregation inhibitory activities in vitro, with IC50 values as low as 0.61 µM. The inhibitory action extended throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation and preventing ß-sheets aggregation. Furthermore, the candidate compounds demonstrated effective disintegration capabilities against preformed α-Syn oligomers and fibrils. Initial mechanistic investigations indicated that the inhibitors may bind to a specific domain within the fibril, inducing fibril instability and subsequent collapse. This process resulted in the formation of a complex system of aggregates with smaller sizes and monomers. Overall, these findings provide valuable insights into the potential of 4-arylidene curcumin derivatives as therapeutic agents for targeting α-Syn aggregation in PD treatment.

Florfenicol sustained-release granules: an in vitro-in vivo correlation study in pigs.

The objective of this study was to synthesize and characterize pharmaceutical characteristics of florfenicol sustained-release granules (FSRGs) in vitro and in vivo. FSRGs were synthesized using monostearate, polyethylene glycol 4000 and starch. In vitro dissolution profiles were studied using the rotating basket method in pH 1.2 HCl solution and pH 4.3 acetate buffer. Twenty-four male healthy Landrace×Yorkshire pigs were equally divided into three groups and administered a 20 mg/kg i.v bolus of florfenicol solution and dosed orally with FSRGs in the fasting and fed states. The Higuchi model was the best fit for the drug release profile in pH 1.2 and pH 4.3 media, and the mechanism of drug dissolution was governed by both diffusion and dissolution. We established a level A in vitro - in vivo correlation for FSRGs and the in vivo profile of the FSRGs can be estimated by the in vitro drug release.

"Phoenix in Flight": an unique fruit morphology ensures wind dispersal of seeds of the phoenix tree (Firmiana simplex (L.) W. Wight).

BACKGROUND: Many seed plants produce winged diaspores that use wind to disperse their seeds. The morphology of these diaspores is directly related to the seed dispersal potential. The majority of winged diaspores have flat wings and only seeds; however, some angiosperms, such as Firmiana produce winged fruit with a different morphology, whose seed dispersal mechanisms are not yet fully understood. In this study, we observed the fruit development of F. simplex and determined the morphological characteristics of mature fruit and their effects on the flight performance of the fruit. RESULTS: We found that the pericarp of F. simplex dehisced early and continued to unfold and expand during fruit development until ripening, finally formed a spoon-shaped wing with multiple alternate seeds on each edge. The wing caused mature fruit to spin stably during descent to provide a low terminal velocity, which was correlated with the wing loading and the distribution of seeds on the pericarp. When the curvature distribution of the pericarp surface substantially changed, the aerodynamic characteristics of fruit during descent altered, resulting in the inability of the fruit to spin. CONCLUSIONS: Our results suggest that the curved shape and alternate seed distribution are necessary for the winged diaspore of F. simplex to stabilize spinning during wind dispersal. These unique morphological characteristics are related to the early cracking of fruits during development, which may be an adaptation for the wind dispersal of seeds.

Hybrids of polyphenolic acids and xanthone, the potential preventive and therapeutic effects on PD: Design, synthesis, in vitro anti-aggregation of α-synuclein, and disaggregation against the existed α-synuclein oligomer and fibril.

The misfolding and aggregation of α-Syn are the central mechanism linking and facilitating the other pathological mechanisms of PD. Maintaining α-Syn proteostasis by suitable inhibitors is an effective means to prevent PD. Disintegrating the neurotoxic oligomers and fibrils into the normal functional α-Syn by inhibitors is a more efficient way for PD treatment. This work synthesized two series hybrids of polyphenolic acids and xanthone. The hybrids possess a sheet-like conjugated skeleton and higher binding energies with α-Syn residues. Some compounds present well α-Syn aggregation inhibitory activities in vitro (IC50 down to 2.58 µM). The inhibitory action goes throughout the aggregation process from lag to the stationary phase by stabilizing α-Syn proteostasis conformation and preventing ß-sheets aggregation. The candidate compounds with appropriate LogP values (2.02-3.11) present good disintegration abilities against the existed α-Syn oligomers and fibrils. The preliminary mechanism studies suggest that the inhibitors could quickly and randomly bind to the specific site closed to the ß-sheet domain in the fibril, resulting in unstable and collapse of the protein fibril, yielding a complex system with aggregates of different sizes and monomers.

Amide derivatives of Gallic acid: Design, synthesis and evaluation of inhibitory activities against in vitro α-synuclein aggregation.

Gallic acid (GA), a natural phenolic acid, has received numerous attention because of its anti-oxidative, anti-inflammatory, and anti-cancer activity. More importantly, GA can act as an efficient inhibitor of α-Synuclein (α-Syn) aggregation at early stages. Nevertheless, some evidences suggest that GA is unlikely to cross the blood-brain barrier because of its high hydrophilicity. Hence, GA may not be considered as a promising candidate or entering brain and directly affecting the central nervous system. Accordingly, we have designed and synthesized a series of amide derivatives of GA, some of which possess appropriate lipophilicity and hydrophilicity with LogP (2.09-2.79). Meanwhile, these sheet-like conjugated compounds have good π-electron delocalization and high ability of hydrogen-bond formation. Some compounds have shown better in vitro anti-aggregation activities than GA towards α-Syn, with IC50 down to 0.98 µM. The valid modification strategy of GA is considered an efficient way to discover novel inhibitors of α-Syn aggregation.

Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein aggregation.

Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09 µM. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.

µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects.

Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0.01% of such spider toxins has been explored, and thus there is a great potential for discovery of novel VGSC modulators as useful pharmacological tools or potential therapeutics. In the current study, we identified a novel peptide, µ-TRTX-Ca1a (Ca1a), in the venom of the tarantula Cyriopagopus albostriatus. This peptide consisted of 38 residues, including 6 cysteines, i.e. IFECSISCEIEKEGNGKKCKPKKCKGGWKCKFNICVKV. In HEK293T or ND7/23 cells expressing mammalian VGSCs, this peptide exhibited the strongest inhibitory activity on Nav1.7 (IC50 378 nM), followed by Nav1.6 (IC50 547 nM), Nav1.2 (IC50 728 nM), Nav1.3 (IC50 2.2 µM) and Nav1.4 (IC50 3.2 µM), and produced negligible inhibitory effect on Nav1.5, Nav1.8, and Nav1.9, even at high concentrations of up to 10 µM. Furthermore, this peptide did not significantly affect the activation and inactivation of Nav1.7. Using site-directed mutagenesis of Nav1.7 and Nav1.4, we revealed that its binding site was localized to the DIIS3-S4 linker region involving the D816 and E818 residues. In three different mouse models of pain, pretreatment with Cala (100, 200, 500 µg/kg) dose-dependently suppressed the nociceptive responses induced by formalin, acetic acid or heat. These results suggest that Ca1a is a novel neurotoxin against VGSCs and has a potential to be developed as a novel analgesic.

Pyrazolamide derivatives inhibit α-Synuclein aggregation, disaggregate preformed fibers, and reduce inclusion formation in neuron cells.

α-Syn fibers, the primary cause and central element of Lewy bodies (LB), play a pivotal role in the development of Parkinson's disease (PD). This research aims to identify more potent inhibitors of α-Syn aggregation. A series of N-aryl-3-aryl-pyrazole-5-carboxamide derivatives were designed and synthesized for this purpose. Among them, four candidate compounds, combining pyrazole and polyphenol blocks, were identified through screening, demonstrating good inhibitory effects with IC50 values in the low micromolar range (1.25-4.29 µM). Two candidates exhibited high permeability through the blood-brain barrier. Mechanistic studies using various methods revealed that the candidates preferentially bind to the aggregation-prone domains-proNAC or NAC domains of α-Syn. This binding hinders the conformational transition from random coil/α-helix to ß-sheet, preserving α-Syn proteostasis. As a result, it interferes with α-Syn nuclei formation, prolongs the lag phase, decelerates the elongation phase, and ultimately impedes the formation of α-Syn fibrils. Additionally, the candidates demonstrated promising results in the disaggregation of preformed α-Syn fibers, potentially by binding to specific sites near the ß-sheet domain within fibers. This reduces fiber stability, causing rapid collapse and yielding smaller aggregates and monomers. Crucially, the candidate compounds exhibited significant inhibitory efficacy against α-Syn aggregation within nerve cells with low cytotoxicity. This resulted in a notable inhibition of the formation of LB-like α-Syn inclusions. These compounds show considerable promise as potential therapeutic agents for the prevention and treatment of PD.

[Effect of L-Type Amino Acid Transporter 1 Expression on Clinicopathological Features and Prognosis of Non-Hodgkin's Lymphoma].

OBJECTIVE: To detect the expression of L-type amino acid transporter 1 (LAT1) in non-Hodgkin's lymphoma (NHL) tissues, and analyze its effect on clinicopathological characteristics and prognosis of patients. METHODS: A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected. The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features (including sex, Ann Arbor stage, extranodal infiltration, Ki-67). The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression. Receiver operating characteristic (ROC) curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality, and analyzing the effect of percentage of LAT1-positive cells on survival rate. RESULTS: LAT1 was positively expressed in NHL tissue. The high expression rate of LAT1 in Ann Arbor stage III and IV groups were higher than that in Ann Arbor stage I group, that in extranodal infiltration group was higher than non-extranodal infiltration group, and that in Ki-67 positive expression group was higher than Ki-67 negative expression group (all P < 0.05). The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%, which was lower than 91.2% in low-LAT1 expression group (P < 0.05). Ann Arbor stage III and IV, extranodal invasion, Ki-67 positive expression and increased expression of LAT1 (LAT1-positive cell percentage score ≥2) were risk factors for mortality. The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%, and the area under the ROC curve was 0.905 (95%CI: 0.897-0.924). The 3-year survival rate of high-LAT1 level group (the percentage of LAT1-positive cells≥45.6%) was 50.00%, which was lower than 78.26% of low-LAT1 level group (P < 0.05). CONCLUSION: The expression level of LAT1 in NHL tissue increases, which affects Ann Arbor stage and extranodal infiltration of patients. LAT1 is a risk factor for death.

Diastereoselective oxidative α-amination of aliphatic aldehydes catalyzed by iodine: synthesis of syn-γ-hydroxy-α-amino acetals.

Aldehydes can react with secondary amines to give α-amino acetals via the α-amination of aliphatic aldehydes catalyzed by iodine. The presence of an asymmetric hydroxylated center at the γ-position of the aldehyde was found to induce the stereoselective amino group. This method represents a stereoselective α-amination of γ-hydroxyaldehydes for the synthesis of syn-γ-hydroxy-α-amino acetals in good yields and reasonable diastereoselectivities under very mild conditions.

Identification and analysis of seven H2O2-responsive miRNAs and 32 new miRNAs in the seedlings of rice (Oryza sativa L. ssp. indica).

Plant microRNAs (miRNAs) have been shown to play critical roles in regulating gene expression at the post-transcriptional level. In this study, we employed high throughput sequencing combined with computational analysis to survey miRNAomes from the seedlings of rice under normal conditions and treatments of H(2)O(2) that result in oxidative stress. Comparison of the miRNAomes and subsequent northern blot analysis identified seven miRNA families differentially expressed under H(2)O(2) stress. Predicted and experimentally validated targets of these H(2)O(2)-responsive miRNAs are involved in different cellular responses and metabolic processes including transcriptional regulation, nutrient transport, auxin homeostasis, cell proliferation and programmed cell death. This indicates that diverse miRNAs form a complex regulatory network to coordinate plants' responses under oxidative stress. In addition, we also discovered 32 new miRNAs in the seedlings of rice. Interestingly, of these new miRNAs, miR3981 was originally found to be a putative exonic miRNA located in the exon of AK106348, suggesting that plants may also use some exons as an miRNA source. This study is the first genome-wide investigation of H(2)O(2)-regulated miRNAs in plants and broadens our perspectives on the important regulatory roles of miRNAs in plant oxidative stress and physiological adaption.

Toxicity mechanism of peri-implantation pesticide beta-cypermethrin exposure on endometrial remodeling in early pregnant mice.

Beta-cypermethrin (ß-CYP) is a universally used pyrethroid pesticide with adverse effects on human health. ß-CYP may impair endometrial remodeling in mice; however, the mechanism remains largely unknown. Endometrial remodeling plays a vital role in embryonic development and the maintenance of pregnancy. Therefore, we explored the mechanism by which peri-implantation ß-CYP administration reduces uterine remodeling in pregnant mice. The C57BL/6 J pregnant mice were administered a dose of 20 mg/kg.bw. d ß-CYP via oral gavage once daily from day 1 of gestation (GD1) to GD7. Molecular markers of endometrial remodeling, stromal cell proliferation, cell cycle regulation, and the PI3K/Akt/mTOR signaling pathway were evaluated in the decidual tissue of the uterus on GD7. An in vivo pseudopregnancy mouse model, a pregnant mouse model treated with an mTOR activator and an mTOR inhibitor and an in vitro decidualization model of mouse endometrial stromal cells were used to confirm ß-CYP-induced defective endometrial remodeling and the key molecules expression of PI3K/Akt/mTOR signaling pathway. The results showed that ß-CYP decreased the expression of the endometrial remodeling markers MMP9 and LIF in the uterine decidua. Peri-implantation ß-CYP treatment markedly downregulated the expression of endometrial proliferation markers PCNA and Ki67 and decreased decidua thickness. Correspondingly, peri-implantation ß-CYP exposure upregulated the expression of FOXO1, P57 and p-4E-BP1 in the decidua. Further experiments showed ß-CYP significantly inhibited key molecules in the PI3K/Akt/mTOR pathway: PI3K, p-Akt/Akt, p-mTOR, and p-P70S6K in the uterine decidua. Additional experiments showed that aberrant endometrial remodeling induced by ß-CYP was aggravated by rapamycin (an mTOR inhibitor) and partially reversed by MHY1485 (an mTOR agonist). In summary, our results indicated that a reduction in the PI3K/Akt/mTOR pathway may enhance defective endometrial remodeling by downregulating the proliferation and differentiation of endometrial stromal cells in early pregnant mice exposed to ß-CYP. Our study elucidates the mechanism of defective endometrial remodeling induced by peri-implantation ß-CYP exposure.

Single cell RNA sequencing reveals mesenchymal heterogeneity and critical functions of Cd271 in tooth development.

BACKGROUND: Accumulating evidence suggests that the maxillary process, to which cranial crest cells migrate, is essential to tooth development. Emerging studies indicate that Cd271 plays an essential role in odontogenesis. However, the underlying mechanisms have yet to be elucidated. AIM: To establish the functionally heterogeneous population in the maxillary process, elucidate the effects of Cd271 deficiency on gene expression differences. METHODS: p75NTR knockout (Cd271-/-) mice (from American Jackson laboratory) were used to collect the maxillofacial process tissue of p75NTR knockout mice, and the wild-type maxillofacial process of the same pregnant mouse wild was used as control. After single cell suspension, the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system. Finally, the sequencing data in Fastq format were obtained. The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data. The gene expression matrix is read by R software, and Seurat is used to control and standardize the data, reduce the dimension and cluster. We search for marker genes for subgroup annotation by consulting literature and database; explore the effect of p75NTR knockout on mesenchymal stem cells (MSCs) gene expression and cell proportion by cell subgrouping, differential gene analysis, enrichment analysis and protein-protein interaction network analysis; understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis. Last we verified the findings single cell sequencing in vitro. RESULTS: We identified 21 cell clusters, and we re-clustered these into three subclusters. Importantly, we revealed the cell-cell communication networks between clusters. We clarified that Cd271 was significantly associated with the regulation of mineralization. CONCLUSION: This study provides comprehensive mechanistic insights into the maxillary- process-derived MSCs and demonstrates that Cd271 is significantly associated with the odontogenesis in mesenchymal populations.

Hybrids of polyphenolic/quinone acids, the potential preventive and therapeutic drugs for PD: Disaggregate α-Syn fibrils, inhibit inclusions, and repair damaged neurons in mice.

Neurotoxic α-Syn fibers, the main components of Lewy bodies, play a key role in the development of PD characterized by a progressive loss of dopaminergic neurons. Here, we designed and synthesized the hybrids of polyphenolic/quinone acids. The candidate compounds showed high α-Syn aggregation inhibitory activities in vitro with IC50 down to 1.6 µM. The inhibition went through the aggregation process by stabilizing the conformation of α-Syn proteostasis and preventing ß-sheets aggregation, especially in the lag phase. Furthermore, the candidate drugs could disintegrate the preformed varisized aggregates into pony-size aggregates and functional monomers and continually inhibit the re-aggregation. The activities of anti-aggregation and aggregates depolymerization result in the reduction of inclusions in neuron cells. The candidate drugs also show high anti-oxidation and low cytotoxicity. They finally repair the damaged neurons in 6-OHDA-lesioned C57 mice and significantly improve PD-like symptoms of the PD model mice. The hybrids are promising molecules for PD prevention and therapy.© 2022 Elsevier Masson SAS. All rights reserved.

D-ring modified novel isosteviol derivatives: design, synthesis and cytotoxic activity evaluation.

A series of polyhydric, amino alcohol and tricyclic derivatives were facilely synthesized by D-ring modification of isosteviol. These compounds were screened for their cytotoxic activities against four human tumor cell lines in vitro. Among them, the 15-α-aminomethyl-16-ß-hydroxyl isosteviol 23 exhibits significant cytotoxicity superior to the positive control (cisplatin) against EC9706, PC-3 and HCT-116 cell lines.

Isolation, structural elucidation, and cytotoxicity of three new ent-kaurane diterpenoids from Isodon japonica var. glaucocalyx.

Three new ENT-kaurane diterpenoids, glaucocalyxin H ( 1), glaucocalyxin I ( 2), and glaucocalyxin J ( 3), together with four known diterpenoids ( 4- 7), were isolated from the leaves of Isodon japonica Hara var. glaucocalyx. Their structures were elucidated by spectroscopic analysis, and the structures of compounds 2 and 3 were further confirmed by X-ray crystallographic analysis. Compounds 1, 4, and 5 were evaluated for their cytotoxicity IN VITRO against CE-1, U87, A-549, MCF-7, Hela, K-562, and HepG-2 human tumor cell lines. Compound 1 showed potent inhibitory activities against six tumor cell lines with IC (50) values ranging from 1.86-10.95 µM, and compounds 4 and 5 exhibited significant selective cytotoxicity on seven tumor cell lines.