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BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in the biology of colorectal cancer (CRC). There are several lncRNAs associated with invasion and metastasis have been characterized in CRC. However, studies focusing on the precise molecular mechanisms by which lncRNAs function in lymph node (LN) metastasis in CRC are still limited. METHODS: In this study, by analyzing TCGA dataset, we identified that AC244100.2 (termed CCL14-AS), a novel lncRNA enriched in the cytoplasm, was negatively correlated with LN metastasis and unfavorable prognosis of CRC. In situ hybridization was used to examine CCL14-AS expression in clinical CRC tissues. Various functional experiments including migration assay and wound-healing assay were used to investigate the effects of CCL14-AS on CRC cells migration. The nude mice popliteal lymph node metastasis model assay further confirmed the effects of CCL14-AS in vivo. RESULTS: CCL14-AS expression was significantly downregulated in CRC tissues compared to adjacent normal tissues. In addition, low CCL14-AS expression was correlated with advanced T classification, LN metastasis, distant metastasis, and shorter disease-free survival of CRC patients. Functionally, CCL14-AS overexpression inhibited the invasiveness of CRC cells in vitro and LN metastasis in nude mice. On the contrary, knockdown of CCL14-AS promoted the invasiveness and LN metastasis abilities of CRC cells. Mechanistically, CCL14-AS downregulated the expression of MEP1A via interacting with MEP1A mRNA and reduced its stability. Overexpression of MEP1A rescued the invasiveness and LN metastasis abilities in CCL14-AS-overexpressing CRC cells. Moreover, the expression levels of CCL14-AS was negatively correlated with that of MEP1A in CRC tissues. CONCLUSIONS: We identified a novel lncRNA, CCL14-AS, as a potential tumor suppressor in CRC. Our findings supported a model in which the CCL14-AS/MEP1A axis serves as critical regulator in CRC progression, suggesting a novel biomarker and therapeutic target in advanced CRC.
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BACKGROUND: Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC. METHODS: Oncomine network and The Cancer Genome Atlas (TCGA) database were downloaded and Gene Set Enrichment Analysis (GSEA) was performed to compare the UBN2's expression between normal and tumor tissues, as well as the potential correlation of UBN2 expression with signaling pathways. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to determine the expression of UBN2 in CRC tissues or cell lines. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of UBN2 on the development and progression of CRC. RESULTS: The analysis of UBN2 expression using Oncomine network showed that UBN2 was upregulated in CRC tissues compared to matched adjacent normal intestinal epithelial tissues. IHC, qRT-PCR and Western blotting confirmed that UBN2 expression is higher in CRC tissues compared with matched adjacent normal intestinal epithelial tissues. In addition, analyses of TCGA data revealed that high UBN2 expression was associated with advanced stages of lymph node metastasis, distant metastasis, and short survival time in CRC patients. IHC showed that high UBN2 expression is correlated with advanced stages of CRC. Moreover, UBN2 is highly expressed in the liver metastatic lesions. Furthermore, knockdown of UBN2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway. CONCLUSION: The current study demonstrates that UBN2 promotes tumor progression in CRC. UBN2 may be used as a promising biomarker for predicting the prognosis of CRC patients.
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Influenza A virus (IAV) is an important pathogen that poses a severe threat to the health of humans. Nucleoprotein (NP) of IAV plays crucial roles in the viral life cycle by interacting with various cellular factors. Histone Acetyl Transferase TIP60 is a key target of several viral proteins during infection, including HIV-1 Tat, HPV E6, HTLV-1 p30II and HCMV UL27 proteins. However, Whether the interaction between the IAV NP and TIP60, and the role of TIP60 in IAV life cycle are largely unknown. Here, we showed that IAV infection up-regulated TIP60 protein and RNA expression. Overexpression of TIP60 inhibited viral protein and RNA expression and reduced the progeny viral titer. Further study revealed that TIP60 inhibited viral replication through activation of TBK1-IRF3 signaling pathway. Furthermore, we demonstrated that the NP protein of IAV interacted with TIP60. Together, these results indicate that TIP60 play a repressor in IAV infection, and it may be a possible target for antiviral drugs.
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Interacciones Huésped-Patógeno , Virus de la Influenza A/fisiología , Lisina Acetiltransferasa 5/metabolismo , Proteínas de Unión al ARN/metabolismo , Transducción de Señal , Proteínas del Núcleo Viral/metabolismo , Replicación Viral , Células A549 , Replicación del ADN , Células HEK293 , Humanos , Virus de la Influenza A/genética , Gripe Humana , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/metabolismo , Lisina Acetiltransferasa 5/genética , Proteínas de la Nucleocápside , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Unión al ARN/genética , Regulación hacia Arriba , Proteínas del Núcleo Viral/genéticaRESUMEN
Semantic processing, a core of language comprehension, involves the activation of brain regions dispersed extensively across the frontal, temporal, and parietal cortices that compose the semantic network. To comprehend the functional structure of this semantic network and how it prepares for semantic processing, we investigated its intrinsic functional connectivity (FC) and the relation between this pattern and semantic processing ability in a large sample from the Human Connectome Project (HCP) dataset. We first defined a well-studied brain network for semantic processing, and then we characterized the within-network connectivity (WNC) and the between-network connectivity (BNC) within this network using a voxel-based global brain connectivity (GBC) method based on resting-state functional magnetic resonance imaging (fMRI). The results showed that 97.73% of the voxels in the semantic network displayed considerably greater WNC than BNC, demonstrating that the semantic network is a fairly encapsulated network. Moreover, multiple connector hubs in the semantic network were identified after applying the criterion of WNC > 1 SD above the mean WNC of the semantic network. More importantly, three of these connector hubs (i.e., the left anterior temporal lobe, angular gyrus, and orbital part of the inferior frontal gyrus) were reliably associated with semantic processing ability. Our findings suggest that the three identified regions use WNC as the central mechanism for supporting semantic processing and that task-independent spontaneous connectivity in the semantic network is essential for semantic processing.
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Encéfalo , Comprensión , Conectoma , Imagen por Resonancia Magnética , Red Nerviosa , Vías Nerviosas , Semántica , Humanos , Imagen por Resonancia Magnética/métodos , Conectoma/métodos , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Adulto , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Masculino , Comprensión/fisiología , Vías Nerviosas/fisiología , Femenino , Adulto Joven , Mapeo Encefálico/métodosRESUMEN
Despite the approval of immune checkpoint blockade (ICB) therapy for various tumor types, its effectiveness is limited to only approximately 15% of patients with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) colorectal cancer (CRC). Approximately 80%-85% of CRC patients have a microsatellite stability (MSS) phenotype, which features a rare T-cell infiltration. Thus, elucidating the mechanisms underlying resistance to ICB in patients with MSS CRC is imperative. In this study, we demonstrate that ubiquitin-specific peptidase 4 (USP4) is upregulated in MSS CRC tumors and negatively regulates the immune response against tumors in CRC. Additionally, USP4 represses the cellular interferon (IFN) response and antigen presentation and impairs PRR signaling-mediated cell death. Mechanistically, USP4 impedes the nuclear localization of interferon regulator Factor 3 (IRF3) by deubiquitinating the K63-polyubiquitin chain of TRAF6 and IRF3. Knockdown of USP4 enhances the infiltration of T cells in CRC tumors and overcomes ICB resistance in an MC38 syngeneic mouse model. Moreover, published datasets revealed that patients showing higher USP4 expression exhibited decreased responsiveness to anti-PD-L1 therapy. These findings highlight an essential role of USP4 in the suppression of antitumor immunity in CRC.
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Neoplasias Encefálicas , Neoplasias Colorrectales , Interferones , Síndromes Neoplásicos Hereditarios , Animales , Ratones , Humanos , Interferones/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Inestabilidad de Microsatélites , Enzimas Desubicuitinizantes/genética , Factor 3 Regulador del Interferón/genética , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
Photoreactions of isoquinoline-1,3,4-triones and oxazoles with different substituents were found to give different chemo-, regio- and diastereoselectivities. The substituent at the C5 on the oxazole ring showed great influence on the chemoselectivity of the photoreaction as well as on the transformation of the photocycloadducts. The 2-methyl-5-methoxyoxazoles reacted with isoquinoline-1,3,4-triones rapidly and gave spirooxetanes with high regio- and diastereo-selectivity. Diastereoselectivity in the reaction of 2-phenyl-5-methoxyoxazoles with isoquinoline-1,3,4-triones was relevant to the substituent on the 4-position on the oxazole ring. Replacement of the 5-methoxy group with 5-methyl or 5-phenyl resulted in significant decrease on the reactivity of the oxazole as well as change on the diastereoselectivity in photocycloaddition with isoquinoline-1,3,4-triones. Acid-mediated transformations of the photocycloadduct spirooxetanes was found to give different type of products including ß-hydroxy-α-aminocarbonyl compounds and spiroisoquinolineoxazolines under different reaction conditions. Substituents on the spirooxetanes as well as the type and amount of acid used in the reaction played important roles in determining the type and diastereoselectivity of the products in the transformations.
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Isoquinolinas/química , Oxazoles/química , Ciclización , Modelos Moleculares , Estructura Molecular , Procesos Fotoquímicos , EstereoisomerismoRESUMEN
Small molecules which can modulate endogenous microRNAs are important chemical tools to study microRNA regulational network. In this Letter we screened the [2+2] photocycloadducts of 2-methoxy-1,4-naphthalenequinone with a series of aryl acetylenes on their activity to modulate endogenous microRNAs. A potent inhibitor of the muscle-specific miR-1 which is closely related with cardiac development and disease was identified. The small molecular inhibitor was the cyclobutene type product derived from the photocycloaddition of 2-methoxy-1,4-naphthalenequinone with tert-butyl (5-(phenylethynyl)quinolin-8-yl) carbonate. Analogues of the small molecular inhibitor were then prepared using similar photocycloaddition reactions for evaluation on inhibition activity on miR-1 to provide structure-activity relationship of the miR-1 inhibitor.
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Alquinos/farmacología , MicroARNs/antagonistas & inhibidores , Naftalenos/farmacología , Alquinos/química , Animales , Línea Celular Tumoral , Humanos , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Naftalenos/química , Procesos Fotoquímicos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Relación Estructura-ActividadRESUMEN
Photocycloaddition, along with subsequent transformation of the photocycloadducts, provides expeditious ways to construct various structures. The photo-induced reactions of α-diketones have been reported to proceed via different reaction pathways with the involvement of one or two of the carbonyl groups. Photoinduced reactions of cyclic α-diketones including N-acetylisatin, phenanthrenequinone and isoquinolinetrione with different C=C containing compounds could take place via [2 + 2], [4 + 2] or [4 + 4] photocycloaddition pathways. We have investigated the photoreactions of these cyclic α-diketones with different types of alkenes and alkynes, with a focus on the unusual cascade reactions initiated by the photocycloaddition reactions of these cyclic α-diketones and the applications of these photocycloaddition reactions along with the transformation of the photocycloadducts. In this paper, we discuss the diverse photo-cycloaddition pathways found in the photocycloaddition of o-diones leading to various photocycloadducts and the potential applications of these reactions via further transformation reactions of the adducts.
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Reacción de Cicloadición , Cetonas/química , Cetonas/síntesis química , Fotoquímica , EstereoisomerismoRESUMEN
Aims: A growing body of evidence demonstrates that Stress granules (SGs), a non-membrane cytoplasmic compartments, are important to colorectal development and chemoresistance. However, the clinical and pathological significance of SGs in colorectal cancer (CRC) patients is unclear. The aim of this study is to propose a new prognostic model related to SGs for CRC on the basis of transcriptional expression. Main methods: Differentially expressed SGs-related genes (DESGGs) were identified in CRC patients from TCGA dataset by limma R package. The univariate and Multivariate Cox regression model was used to construct a SGs-related prognostic prediction gene signature (SGPPGS). The CIBERSORT algorithm was used to assess cellular immune components between the two different risk groups. The mRNA expression levels of the predictive signature from 3 partial response (PR) and 6 stable disease (SD) or progress disease (PD) after neoadjuvant therapy CRC patients' specimen were examined. Key findings: By screening and identification, SGPPGS comprised of four genes (CPT2, NRG1, GAP43, and CDKN2A) from DESGGs is established. Furthermore, we find that the risk score of SGPPGS is an independent prognostic factor to overall survival. Notably, the abundance of immune response inhibitory components in tumor tissues is upregulated in the group with a high-risk score of SGPPGS. Importantly, the risk score of SGPPGS is associated with the chemotherapy response in metastatic colorectal cancer. Significance: This study reveals the association between SGs related genes and CRC prognosis and provides a novel SGs related gene signature for CRC prognosis prediction.
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Gastric cancer (GC) is a heterogeneous disease, threatening millions of lives worldwide, yet the functional roles of long non-coding RNAs (lncRNAs) in different GC subtypes remain poorly characterized. Microsatellite stable (MSS)/epithelial-mesenchymal transition (EMT) GC is the most aggressive subtype associated with a poor prognosis. Here, we apply integrated network analysis to uncover lncRNA heterogeneity between GC subtypes, and identify MIR200CHG as a master regulator mediating EMT specifically in MSS/EMT GC. The expression of MIR200CHG is silenced in MSS/EMT GC by promoter hypermethylation, associated with poor prognosis. MIR200CHG reverses the mesenchymal identity of GC cells in vitro and inhibits metastasis in vivo. Mechanistically, MIR200CHG not only facilitates the biogenesis of its intronic miRNAs miR-200c and miR-141, but also protects miR-200c from target-directed miRNA degradation (TDMD) through direct binding to miR-200c. Our studies reveal a landscape of a subtype-specific lncRNA regulatory network, providing clinically relevant biological insights towards MSS/EMT GC.
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Transición Epitelial-Mesenquimal , MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/patología , Estabilidad del ARNRESUMEN
Direct C-H functionalization of various enamides and enecarbamates was realized through visible-light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)(2)(dtbbpy)PF(6)] as photocatalyst in combination with Na(2)HPO(4), enamides such as N-vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2-bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal C=C double bond in the E configuration could not be alkylated. Alkylation of N-vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N-vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron-deficient bromides such as 3-bromoacetyl acetate with N-vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized C=C double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.
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Amidas/química , Carbamatos/química , Iridio/química , Luz , Compuestos Organometálicos/química , Catálisis , Estructura Molecular , Oxidación-Reducción , Procesos FotoquímicosRESUMEN
As a key area in word reading, the left ventral occipitotemporal cortex is proposed for abstract orthographic processing, and its middle part has even been labeled as the visual word form area. Because the definition of the VWFA largely varies and the reading task differs across studies, the function of the left ventral occipitotemporal cortex in word reading is continuingly debated on whether this region is specific for orthographic processing or be involved in an interactive framework. By using representational similarity analysis (RSA), this study examined information representation in the VWFA at the individual level and the modulatory effect of reading task. Twenty-four subjects were scanned while performing the explicit (i.e., the naming task) and implicit (i.e., the perceptual task) reading tasks. Activation analysis showed that the naming task elicited greater activation in regions related to phonological processing (e.g., the bilateral prefrontal cortex and temporoparietal cortex), while the perceptual task recruited greater activation in visual cortex and default mode network (e.g., the bilateral middle frontal gyrus, angular gyrus, and the right middle temporal gyrus). More importantly, RSA also showed that task modulated information representation in the bilateral anterior occipitotemporal cortex and VWFA. Specifically, ROI-based RSA revealed enhanced orthographic and phonological representations in the bilateral anterior fusiform cortex and VWFA in the naming task relative to the perceptual task. These results suggest that lexical representation in the VWFA is influenced by the demand of phonological processing, which supports the interactive account of the VWFA.
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Mapeo Encefálico , Reconocimiento Visual de Modelos , Mapeo Encefálico/métodos , Humanos , Imagen por Resonancia Magnética , Reconocimiento Visual de Modelos/fisiología , Lectura , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiologíaRESUMEN
Background: Forkhead box S1 (FOXS1) is a member of the forkhead box (FOX) transcriptional factor superfamily. The biological roles and underlying regulatory mechanism of FOXS1 in CRC remain unclear. Methods: Bioinformatics analysis, Western blotting, real-time PCR, and immunohistochemistry (IHC) were used to detect the expression FOXS1 in CRC. MTT assay, transwell assay, human umbilical vein endothelial cell tube formation assay, and chicken chorioallantoic membrane assay were performed to investigate the effects of FOXS1 on proliferation, invasion, and angiogenesis. Additionally, tumor formation assay and orthotopic implantation assay were used to investigate the effects of FOXS1 on tumor growth and metastasis in vivo. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the correlation between FOXS1 and EMT or angiogenesis. The correlation between FOXS1 and CXCL8 expression was analyzed in clinical CRC samples using IHC. Results: The results showed that FOXS1 expression was upregulated in CRC tissues compared with adjacent normal intestine tissues. A high FOXS1 expression is positively correlated with poor survival. FOXS1 promoted the malignant behavior of CRC cancer cells in vitro, including proliferation, invasion, and angiogenesis. In addition, FOXS1 promoted tumor growth and metastasis in nude mice. Mechanistically, FOXS1 upregulated the expression of C-X-C motif chemokine ligand 8 (CXCL8) at the transcriptional level. Knockdown of CXCL8 blocked FOXS1 induced the enhancement of the EMT and angiogenesis. GSEAs in public CRC datasets revealed strong correlations between FOXS1 expression and EMT marker and angiogenesis markers. IHC showed that FOXS1 expression was positively correlated with CXCL8 expression and CD31 expression in clinical CRC samples. Conclusion: The results suggest that FOXS1 promotes angiogenesis and metastasis by upregulating CXCL8 in CRC. Interference with the FOXS1/CXCL8 axis may serve as a potential therapeutic target for the treatment of metastatic CRC.
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Drought is the abiotic factor that adversely affects plant growth, development survival, and crop productivity, posing a substantial threat to sustainable agriculture worldwide, especially in warm and dry areas. However, the extent of damage depends upon the crop growth stage, severity and frequency of the stress. In general, the reproductive growth phase is more sensitive to stresses causing a substantial loss in crop productivity. Saccharum spontaneum (L.) is the most variable wild relative of sugarcane with potential for use in sugarcane crop improvement programs. In the present study addresses the transcriptomic analysis of drought stress imposed by polyethylene glycol-6000 (PED-6000; w/v- 25%) on the root tip tissues of S. spontaneum GX83-10. The analysis of microarrays of drought-stressed roots was performed at 0 (CK), 2 (T2), 4 (T4), 8 (T8) and 24 h (T24). The analyzed data were compared with the gene function annotations of four major databases, such as Nr, KOG/COG, Swiss-Prot, and KEGG, and a total of 62,988 single-gene information was obtained. The differently expressed genes of 56237 (T4), 59319 (T8), and 58583 (T24), among which CK obtained the most significant number of expressed genes (35920) as compared to T24, with a total of 53683 trend genes. Gene ontology (GO) and KEGG analysis were performed on the 6 important trends, and a total of 598 significant GO IDs and 42 significantly enriched metabolic pathways. Furthermore, these findings also aid in the selection of novel genes and promoters that can be used to potentially produce crop plants with enhanced stress resistance efficiency for sustainable agriculture.
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Indoleamine 2,3 dioxygenase 1 (IDO1) is an attractive target for cancer immunotherapy. However, IDO1 inhibitors have shown disappointing therapeutic efficacy in clinical trials, mainly because of the activation of the aryl hydrocarbon receptor (AhR). Here, we show a post-transcriptional regulatory mechanism of IDO1 regulated by a proteasome-associated deubiquitinating enzyme, USP14, in colorectal cancer (CRC). Overexpression of USP14 promotes tryptophan metabolism and T-cell dysfunction by stabilizing the IDO1 protein. Knockdown of USP14 or pharmacological targeting of USP14 decreases IDO1 expression, reverses suppression of cytotoxic T cells, and increases responsiveness to anti-PD-1 in a MC38 syngeneic mouse model. Importantly, suppression of USP14 has no effects on AhR activation induced by the IDO1 inhibitor. These findings highlight a relevant role of USP14 in post-translational regulation of IDO1 and in the suppression of antitumor immunity, suggesting that inhibition of USP14 may represent a promising strategy for CRC immunotherapy.
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Neoplasias Colorrectales , Receptores de Hidrocarburo de Aril , Animales , Neoplasias Colorrectales/genética , Enzimas Desubicuitinizantes , Indolamina-Pirrol 2,3,-Dioxigenasa , Ratones , Complejo de la Endopetidasa Proteasomal , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Triptófano/metabolismo , Ubiquitina TiolesterasaRESUMEN
Photocycloaddition of isoquinoline-1,3,4-trione and 5-methoxyoxazoles affords spiroisoquinolineoxetanes with high regio- and diastereoselectivity. The spiroisoquinolineoxetanes can be conveniently converted into novel spiroisoquinolineoxazoline derivatives through acid catalyzed sequential reactions.
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In the isoquinoline ring system of the title mol-ecule, C(18)H(20)N(2)O(5)S, the fused N-heterocyclic ring is distorted towards a half-boat conformation. The methyl formate moiety is disordered over two sets of sites with refined occupancies of 0.882â (5) and 0.118â (5). In the crystal, mol-ecules are linked via weak inter-molecular C-Hâ¯O hydrogen bonds into one-dimensional chains along [010].
RESUMEN
In the isoquinoline ring system of the title mol-ecule, C(18)H(20)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-aza-spiro ring is essentially planar, with a maximum deviation of 0.029â (1)â Å, and makes a dihedral angle of 30.63â (5)° with the benzene ring. The mol-ecular structure is stabilized by a weak intra-molecular C-Hâ¯O hydrogen bond, which generates a S(6) ring motif. In the crystal, mol-ecules are linked via weak inter-molecular C-Hâ¯O hydrogen bonds into a three-dimensional supra-molecular network. Additional stabilization is provided by π-π stacking inter-actions between symmetry-related benzene rings with a centroid-centroid distance of 3.6507â (5)â Å.
RESUMEN
In the isoquinoline ring system of the title compound, C(19)H(22)N(2)O(5), the N-heterocyclic ring is in a half-chair conformation. The dioxa-2-aza-spiro ring is essentially planar [maximum deviation of 0.025â (1)â Å] and forms a dihedral angle of 23.51â (5)° with the benzene ring. In the crystal, mol-ecules are linked via weak inter-molecular C-Hâ¯O and C-Hâ¯N hydrogen bonds into chains along [010].
RESUMEN
In the isoquinoline ring system of the title mol-ecule, C(22)H(20)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-aza-spiro ring is essentially planar [maximum deviation = 0.026â (1)â Å] and forms dihedral angles of 22.53â (5) and 64.46â (5)° with the benzene and phenyl rings, respectively. The mol-ecular structure is stabilized by a weak intra-molecular C-Hâ¯O hydrogen bond, which generates an S(7) ring motif. In the crystal, mol-ecules are linked via weak inter-molecular C-Hâ¯O and C-Hâ¯N hydrogen bonds into layers parallel to (102).