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1.
Fitoterapia ; 173: 105793, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38158161

ABSTRACT

Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Structurally, phometide A (1) represented the first example of C12 polyketide characterized by an unusual tetrahydrobenzofuran-3(2H)-one core with an α,ß-unsaturated ketone functionality, while phometide B (2) was an unprecedented molecule containing a 2-pentylcycloheptan-1-one scaffold. In an antimicrobial activity assay, phometide A (1) exhibited significant inhibitory activity against Staphylococcus aureus with MIC value of 4 µg/mL. Phometide B (2) showed moderate antifungal activity against Candida albicans with an MIC value of 16 µg/mL. Furthermore, compounds 1 and 2 were evaluated for their acetylcholinesterase inhibitory and cytotoxic activities.


Subject(s)
Gastrodia , Polyketides , Molecular Structure , Phoma , Acetylcholinesterase , Circular Dichroism
2.
Org Lett ; 25(10): 1711-1716, 2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36892283

ABSTRACT

Herein, we described a highly regio- and enantioselective Friedel-Crafts alkylation of aniline derivatives with in situ generated ortho-quinone methides enabled by chiral phosphoric acid, furnishing a wide range of enantioenriched triarylmethanes bearing three similar benzene rings in high yields (up to 98%) with excellent stereoselectivities (up to 98% ee). Furthermore, the large-scale reactions and diversified transformations of product demonstrate the practicality of the protocol. Density functional theory calculations elucidate the origin of the enantioselectivity.

3.
Org Biomol Chem ; 19(39): 8607-8612, 2021 10 14.
Article in English | MEDLINE | ID: mdl-34569587

ABSTRACT

The chiral keto-substituted propargylamines are an essential class of multifunctional compounds in the field of organic and pharmaceutical synthesis and have attracted considerable attention, but the related synthetic approaches remain limited. Therefore, a concise and efficient method for the enantioselective synthesis of ß-keto propargylamines via chiral phosphoric acid-catalyzed asymmetric Mannich reaction between ß-keto acids and C-alkynyl N-Boc N,O-acetals as easily available C-alkynyl imine precursors has been demonstrated here, affording a broad scope of ß-keto N-Boc-propargylamines in high yields (up to 97%) with generally high enantioselectivities (up to 97 : 3 er).

4.
J Nat Prod ; 83(11): 3471-3475, 2020 11 25.
Article in English | MEDLINE | ID: mdl-33180498

ABSTRACT

Penisarins A (1) and B (2), sesquiterpene coumarins with an unusual tricyclic sesquiterpene system, were isolated from endophytic Penicillium sp. KMU18029. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 2 showed significant cytotoxicities against two human cancer cell lines, HL-60 and SMMC-7721, with IC50 values of 3.6 ± 0.2 and 3.7 ± 0.2 µM, respectively.


Subject(s)
Coumarins/isolation & purification , Penicillium/chemistry , Sesquiterpenes/isolation & purification , Cell Line, Tumor , Circular Dichroism , Coumarins/chemistry , Crystallography, X-Ray , Humans , Molecular Structure , Sesquiterpenes/chemistry
5.
Med Sci Monit ; 26: e926669, 2020 Sep 19.
Article in English | MEDLINE | ID: mdl-32948737

ABSTRACT

BACKGROUND The aim of this study was to analyze the risk factors of pressure injury (PI) in critically ill patients with cancer to build a risk prediction model for PI. MATERIAL AND METHODS Between January 2018 and December 2019, a total of 486 critically ill patients with cancer were enrolled in the study. Univariate analysis and binary logistic regression analysis were used to explore risk factors. Then, a risk prediction equation was constructed and a receiver operator characteristic (ROC) curve analysis model was used for prediction. RESULTS Of the 486 critically ill patients with cancer, 15 patients developed PI. Risk factors found to have a significant impact on PI in critically ill patients with cancer included the APACHE II score (P<0.001), semi-reclining position (P=0.006), humid environment/moist skin (P<0.001), and edema (P<0.001). These 4 independent risk factors were used in the regression equation, and the risk prediction equation was constructed as Z=0.112×APACHE II score +2.549×semi-reclining position +2.757×moist skin +1.795×edema-9.086. From the ROC curve analysis, the area under the curve (AUC) was 0.938, sensitivity was 100.00%, specificity was 83.40%, and Youden index was 0.834. CONCLUSIONS The PI risk prediction model developed in this study has a high predictive value and provides a basis for PI prevention and treatment measures for critically ill patients with cancer.


Subject(s)
Models, Biological , Neoplasms/epidemiology , Pressure Ulcer/epidemiology , Aged , China/epidemiology , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors
7.
Curr Comput Aided Drug Des ; 16(3): 222-230, 2020.
Article in English | MEDLINE | ID: mdl-30706826

ABSTRACT

BACKGROUND: B-RafV600E kinase was identified as an important target in current cancer treatment, and the type II B inhibitors show good qualities in preclinical studies. Therefore, it is very important to discover novel II B inhibitors of B-RafV600E kinase. METHODS: In order to discover novel II B inhibitors of B-RafV600E kinase, virtual screening against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3DQSAR model and binding free energy (ΔGbind) calculation studies. The inhibitory activities against A375 cell lines of the hit compounds were tested by using MTT assay. RESULTS: Five promising hit compounds were obtained after screening, and all the five hit compounds showed good inhibitory rates against A375 cell lines. CONCLUSION: The combined approach of the virtual screening in our work is effective, which can be used to discover novel inhibitors with a new skeleton. In addition, the five compounds obtained from the screening showed good inhibitory rates against A375 cell lines, which can be considered to develop new II B inhibitors of B-RafV600E kinase.


Subject(s)
Drug Discovery , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Molecular Docking Simulation , Neoplasms/drug therapy , Neoplasms/metabolism , Proto-Oncogene Proteins B-raf/metabolism , Quantitative Structure-Activity Relationship , Thermodynamics
8.
Onco Targets Ther ; 11: 7635-7642, 2018.
Article in English | MEDLINE | ID: mdl-30464512

ABSTRACT

BACKGROUND: (PD-L2), a ligand of programmed cell death protein 1 (PD-1), is an inhibitory receptor of T cells and activated B cells. Many studies have focused on PD-L1, another ligand of PD-1, and the prognostic significance of PD-L1 has been reported in many tumors. However, the expression of PD-L2 in relation to clinical outcomes has not been fully investigated in cancer patients. PATIENTS AND METHODS: In this study, we investigated the expression of PD-L2 via immunohistochemistry (IHC) in the pathological specimens of 348 patients treated for colorectal cancer (CRC). RESULTS: Strong PD-L2 expression was found in the cancer tissues from 41% of the CRC patients who also had a high TNM stage and carcinoembryonic antigen (CEA) concentration. We also carried out functional studies in vitro, which showed that PD-L2 did not influence the growth of the CRC cell line HCT116, but increased cell invasion. CONCLUSION: Collectively, these findings suggest that PD-L2 may be a potential therapeutic target for CRC.

9.
Oncotarget ; 7(19): 27458-67, 2016 May 10.
Article in English | MEDLINE | ID: mdl-27050275

ABSTRACT

PURPOSE: To examine the function of serum lactic dehydrogenase (SLDH) level after intensity-modulated radiotherapy (IMRT) as a predictive factor for and loco-regional relapse free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS), and overall survival(OS) among patients with in-situ nasopharyngeal carcinoma (NPC). RESULTS: Compared with the normal pt-SLDH group, elevated pt-SLDH demonstrated significant lower DMFS (46 versus 66 months, hazard ratio (HR) 4.07, 95% CI 2.43-6.80, p < 0.001), DFS (46 versus 63 months, HR 2.78, 95% CI 1.70-4.53, p < 0.001), and OS (54 versus 66 months, HR 2.93, 95% CI 1.65-5.23, p < 0.001). Distant metastasis were observed in 32.8% (20/61) patients with elevated pt-SLDH, and 8% (54/678) in normal SLDH (odds ratio (OR) 6.13, 95% CI 3.35-11.18, p < 0.001). COX regression showed that pt-SLDH was an independent prognostic factors for OS (HR 2.91, 95% CI 1.57-5.41, p < 0.001), DMFS (HR 4.21, 95% CI 2.51-7.07, p < 0.001), LRFS (HR 2.53, 95% CI 1.22-5.24, p < 0.001), and DFS (HR 2.81, 95% CI 1.72-4.59, p < 0.001). MATERIALS AND METHODS: The records of 739 in-situ NPC patients admitted to Zhejiang Cancer Hospital between January 2007 and May 2012 were retrospectively reviewed. The relationships between post-treatment SLDH (pt-SLDH) and LRFS, DMFS, DFS, and OS were analyzed. CONCLUSIONS: Our finding indicated that elevated pt-SLDH could be a simple available prognostic indicator for distant metastasis and survival for in-situ NPC patients.


Subject(s)
Carcinoma/enzymology , Carcinoma/radiotherapy , L-Lactate Dehydrogenase/blood , Nasopharyngeal Neoplasms/enzymology , Nasopharyngeal Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Carcinoma/mortality , Carcinoma/pathology , Disease-Free Survival , Female , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Neoplasm Metastasis , Neoplasm Recurrence, Local/enzymology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Survival Analysis , Young Adult
10.
Org Lett ; 16(11): 3044-7, 2014 Jun 06.
Article in English | MEDLINE | ID: mdl-24811051

ABSTRACT

The catalytic enantioselective conjugate addition of acetaldehyde to polyconjugated substrates, nitrodienynes and nitroenynes, has been accomplished using organocatalysis. Various functionalized 1,3-enynes and propargylic compounds were obtained in moderate to good yields with high enantioselectivity. The synthetic utilities of the conjugate addition reactions have been highlighted in the concise total synthesis of (+)-α-lycorane and the metal-free synthesis of chiral ß-alkynyl acids.


Subject(s)
Acetaldehyde/chemistry , Alkynes/chemistry , Alkynes/chemical synthesis , Amaryllidaceae Alkaloids/chemistry , Amaryllidaceae Alkaloids/chemical synthesis , Nitro Compounds/chemistry , Catalysis , Molecular Structure , Stereoisomerism
11.
PLoS One ; 9(3): e91357, 2014.
Article in English | MEDLINE | ID: mdl-24667308

ABSTRACT

The microRNA319 (miR319) family is conserved among diverse plant species. In rice (Oryza sativa L.), the miR319 gene family is comprised of two members, Osa-miR319a and Osa-miR319b. We found that overexpressing Osa-miR319b in rice resulted in wider leaf blades and delayed development. Here, we focused on the biological function and potential molecular mechanism of the Osa-miR319b gene in response to cold stress in rice. The expression of Osa-miR319b was down-regulated by cold stress, and the overexpression of Osa-miR319b led to an enhanced tolerance to cold stress, as evidenced by higher survival rates and proline content. Also, the expression of a handful of cold stress responsive genes, such as DREB1A/B/C, DREB2A, TPP1/2, was increased in Osa-miR319b transgenic lines. Furthermore, we demonstrated the nuclear localization of the transcription factors, OsPCF6 and OsTCP21, which may be Osa-miR319b-targeted genes. We also showed that OsPCF6 and OsTCP21 expression was largely induced by cold stress, and the degree of induction was obviously repressed in plants overexpressing Osa-miR319b. As expected, the down-regulation of OsPCF6 and OsTCP21 resulted in enhanced tolerance to cold stress, partially by modifying active oxygen scavenging. Taken together, our findings suggest that Osa-miR319b plays an important role in plant response to cold stress, maybe by targeting OsPCF6 and OsTCP21.


Subject(s)
Adaptation, Physiological/genetics , Gene Expression Regulation, Plant , Genes, Plant/genetics , MicroRNAs/genetics , Oryza/genetics , Plant Leaves/growth & development , Stress, Physiological/genetics , Cold Temperature , Gene Expression Profiling , Oryza/growth & development , Phenotype , Plant Leaves/anatomy & histology , Plant Leaves/genetics , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development
13.
J Org Chem ; 77(8): 4103-10, 2012 Apr 20.
Article in English | MEDLINE | ID: mdl-22443260

ABSTRACT

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).


Subject(s)
Acetone/chemistry , Alkenes/chemistry , Amines/chemistry , Ketones/chemistry , Catalysis , Hydrogen Bonding , Molecular Structure , Stereoisomerism
14.
Org Lett ; 13(23): 6200-3, 2011 Dec 02.
Article in English | MEDLINE | ID: mdl-22044048

ABSTRACT

Biologically important and synthetically challenging spirocyclopentaneoxindoles with four contiguous stereocenters including one spiroquaternary stereocenter have been constructed in good yields (72-87%) with excellent diastereoselectivity (16:1→30:1 dr) and enantioselectivity (93→99% ee) by a combined Ru-catalyzed cross-metathesis/organocatalyzed asymmetric double-Michael addition sequence.


Subject(s)
Cyclopentanes/chemical synthesis , Indoles/chemical synthesis , Ruthenium/chemistry , Spiro Compounds/chemical synthesis , Catalysis , Combinatorial Chemistry Techniques , Cyclopentanes/chemistry , Indoles/chemistry , Molecular Structure , Oxindoles , Spiro Compounds/chemistry , Stereoisomerism
15.
Org Lett ; 13(23): 6160-3, 2011 Dec 02.
Article in English | MEDLINE | ID: mdl-22050288

ABSTRACT

A highly diastereo- and enantioselective organocatalytic protocol for the synthesis of biologically important spirocyclopentaneoxindoles containing the oxime functional group from easily accessible 3-allyl-substituted oxindoles and nitroolefins has been developed by a one-pot Michael addition/ISOC/fragmentation sequence.


Subject(s)
Cyclopentanes/chemical synthesis , Indoles/chemical synthesis , Oximes/chemistry , Spiro Compounds/chemical synthesis , Catalysis , Cyclization , Cyclopentanes/chemistry , Indoles/chemistry , Molecular Structure , Oxindoles , Spiro Compounds/chemistry , Stereoisomerism
16.
Chem Asian J ; 6(1): 220-5, 2011 Jan 03.
Article in English | MEDLINE | ID: mdl-21077095

ABSTRACT

The first catalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroenynes catalyzed by cinchona alkaloid-based thiourea organocatalysts has been developed. The 1,4-addition adducts were obtained solely, in moderate to good yields (up to 93%) with good enantioselectivities (up to 99% ee). This protocol affords a conceptually different entry to the precursors of pharmaceutically important chiral ß-alkynyl acid derivatives and synthetically useful chiral nitroalkynes. Notably, the protocol worked well with both aryl- and alkyl-substituted alkynyl substrates.


Subject(s)
Alkenes/chemistry , Malonates/chemistry , Thiourea/chemistry , Catalysis , Cinchona Alkaloids/chemistry , Molecular Structure , Stereoisomerism
17.
Cell Immunol ; 236(1-2): 154-60, 2005.
Article in English | MEDLINE | ID: mdl-16188246

ABSTRACT

CD28 is expressed abnormally on human multiple myeloma (MM) cells but the significance had not been identified until now. In this paper, we are suggesting that abnormal expression of CD28 might be a marker of tumour progression. We therefore took the approach of generating a hybridoma cell line capable of secreting agonist monoclonal antibody directed against human CD28 (agonist anti-CD28 mAb) and then determined the expression of CD28 molecules on the MM cell lines U266 and XG1. The biological effects of agonist anti-CD28 mAb on cell growth and proliferation of U266 and XG1 cell lines were then analysed. Our results showed that the expression of CD28 on U266 and XG1 was significantly higher than that of PBTC or Jurkat cells. We found that by adding the agonist anti-CD28 mAb to cultures of U266 and XG1 cells their rate of growth and proliferation was obviously inhibited. Further morphological and molecular analyses found that U266 and XG1 incubated with agonist anti-CD28 mAb showed signs of nuclear condensation, chromatin marginal changes, cells membrane breaking, and cytoplasmic shrinkage. Vacuoles and apoptotic bodies were also observed using a transmission electron microscope and the development of typical DNA laddering patterns were found by the use of electrophoresis assays, suggesting that U266 and XG1 cells were undergoing apoptosis induced by agonist anti-CD28 mAb in vitro.


Subject(s)
Apoptosis/immunology , CD28 Antigens/immunology , Multiple Myeloma/immunology , Animals , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/pharmacology , CD28 Antigens/metabolism , Cell Line, Tumor/physiology , Cell Line, Tumor/ultrastructure , Chromatography, Affinity , Humans , Mice , Mice, Inbred BALB C , Microscopy, Electron, Transmission/methods , Multiple Myeloma/metabolism
18.
Cell Immunol ; 236(1-2): 146-53, 2005.
Article in English | MEDLINE | ID: mdl-16165113

ABSTRACT

B7 family molecules are mainly expressed on the outer membrane of antigen-presenting cells. Here, our results demonstrate that CD80, CD86, and PD-L1 molecules are also expressed on T-cells that have been activated by simultaneous exposure to anti-CD3 and anti-CD28 mAbs, but PD-L2 and GL50 molecules were not detectable during the first six days of culture that follow such stimulation. We have analysed the time course of B7 family molecule expression on activated T-cells. CD28 and its ligands, CD80/CD86, have a high degree of co-localization and exhibit compartmental distribution on the membrane of activated T-cells, which is visualized by confocal microscopy. Interestingly, the co-localization of PD-1 and its ligand also exhibit similar phenomenon. Additionally, we provide evidence indicating that the CD80, CD86, and PD-L1 molecules are functional, since T-cells expressing B7 family molecules are able to stimulate the proliferation of highly purified allogeneic or autologous T-cells. Anti-CD80, anti-CD86, and soluble CD28-Ig protein could significantly attenuate the proliferation of T-cells, whereas anti-PD-L1 mAb may lead to the expansion of activated T-cells. We can conclude that activated T-cells expressing B7 family molecules could act as "APC" to trigger purified T-cells, and B7 family molecules play important roles during the activation of T-cells. These results indicate a need for further work, exploring the regulatory roles these molecules may play in immune responses.


Subject(s)
B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Membrane Glycoproteins/metabolism , Peptides/metabolism , T-Lymphocytes/metabolism , Animals , Antibodies, Monoclonal/pharmacology , Antigens, CD , B7-H1 Antigen , CD28 Antigens/immunology , CD3 Complex/immunology , Cells, Cultured , Humans , Laser Scanning Cytometry/methods , Leukocytes, Mononuclear , Lymphocyte Activation/immunology , Mice
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