RESUMEN
Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of -4.45 kcal mol-1. These results suggested that these compounds might be potential antiviral agents.
Asunto(s)
Quinazolinas , Receptor Toll-Like 7 , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 7/metabolismo , Quinazolinas/química , Simulación del Acoplamiento Molecular , Adyuvantes Inmunológicos , Antivirales/farmacología , Pirimidinas/químicaRESUMEN
Allylic azlactones are greatly significant in terms of potential bioactivities and synthetic applications. Owing to the burgeoning interest of the pharmaceutical industry in α-amino acid derivatives, discovering strategies for the synthesis of allylic azlactones is important. Herein, we establish a transition-metal-free regioselectivity switch of α-amino acid-derived esters and MBH carbonates, which exhibits broad reaction scope and good reaction yields. Control reactions indicate that both base and solvent are important for regioselectivity.
RESUMEN
BACKGROUND: Poly C Binding Protein 1 (PCBP1) belongs to the heterogeneous nuclear ribonucleoprotein family. It is a multifunctional protein that participates in several functional circuits and plays a variety of roles in cellular processes. Although PCBP1 has been identified in several mammals, its function in porcine was unclear. RESULTS: In this study, we cloned the gene of porcine PCBP1 and analyzed its evolutionary relationships among different species. We found porcine PCBP1 protein sequence was similar to that of other animals. The subcellular localization of PCBP1 in porcine kidney cells 15 (PK-15) cells was analyzed by immunofluorescence assay (IFA) and revealed that PCBP1 was mainly localized to the nucleus. Reverse transcription-quantitative PCR (RT-qPCR) was used to compare PCBP1 mRNA levels in different tissues of 30-day-old pigs. Results indicated that PCBP1 was expressed in various tissues and was most abundant in the liver. Finally, the effects of PCBP1 on cell cycle and apoptosis were investigated following its overexpression or knockdown in PK-15 cells. The findings demonstrated that PCBP1 knockdown arrested cell cycle in G0/G1 phase, and enhanced cell apoptosis. CONCLUSIONS: Porcine PCBP1 is a highly conserved protein, plays an important role in determining cell fate, and its functions need further study.
Asunto(s)
Proteínas Portadoras , Proteínas de Unión al ARN , Porcinos , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Apoptosis/fisiología , Unión Proteica , MamíferosRESUMEN
Cyophiobiolins A-D, four unreported ophiobolin-type sesterterpenoids, were isolated from Cytospora rhizophorae A761, an endophytic fungus from Gynochthodes officinalis. The structures of these undescribed compounds were fully characterized on the basis of extensively spectroscopic data (1D, 2D NMR and HRESIMS) and single-crystal X-ray diffraction analyses. Moreover, cyophiobiolins A-D were evaluated for in vitro cytotoxic, anti-inflammatory, and antibacterial activities. Cyophiobiolins A-B showed inhibitory potency against lipopolysaccharide (LPS)-induced oxide production with IC50 values of 66.3 µM and 53.3 µM, respectively.
Asunto(s)
Ascomicetos , Lipopolisacáridos , Antibacterianos/química , Antibacterianos/farmacología , Antiinflamatorios/química , Ascomicetos/química , Lipopolisacáridos/farmacología , Estructura Molecular , Óxidos , SesterterpenosRESUMEN
A two-step protecting-group-free protocol for the synthesis of 3'-hydroxy-5,7-dimethoxy-4-O-2'-cycloflavan (1) and concise total synthesis of 4'-hydroxy-5,7-dimethoxy-4-O-2'-cycloflavan (8) enabled by a PTSA triggered bioinspired olefin isomerization/hemiacetalization/dehydration/[3 + 3]-type cycloaddition cascade reaction are reported. The successful synthesis of cycloflavan 8 along with GIAO 13C NMR calculations of flavan-4-ol 9 and cycloflavan 8 indicated the misassignment of the flavonoid isolated previously and realized the revision of its actual structure.
Asunto(s)
Flavonoides , Polifenoles , Alquenos , Reacción de Cicloadición , Flavonoides/química , Espectroscopía de Resonancia MagnéticaRESUMEN
Foeniculins A-C (1-3) together with a pair of enantiomers (±)-foeniculin D (4) were isolated from endophytic fungus Diaporthe foeniculina BZM-15. Their structures including absolute configurations were unambiguously established by extensive interpretation of the NMR and HR-ESI-MS data, ECD measurements powered by molecular calculations, as well as Mo2(OAc)4 mediated CD methodology. The cytotoxic activity assay disclosed that these compounds didn't show any noticeable cytotoxic activity.[Formula: see text].
Asunto(s)
Ascomicetos , Pironas , Ascomicetos/química , Línea Celular Tumoral , Estructura Molecular , Pironas/químicaRESUMEN
Phytochemical investigation of Diaporthe foeniculina BZM-15 led to one new γ-butyrolactone derivative, diaportone A (1), one cyclopentenone derivative, diaportone B (3), and one monoterpene derivative, diaportone C (5), along with six known compounds (2, 4, and 6-9). Their structures as well as the absolute configurations were characterized by means of NMR, HRESIMS, and ECD spectroscopy and quantum chemistry calculation, respectively. Furthermore, all compounds were evaluated for their cytotoxic activity and antibacterial activity, and compounds 7 and 8 displayed significant antiproliferative effects on three human cancer cell lines (SF-268, MCF-7, and HepG2) with IC50 values ranging from 3.6 to 15.8 µM.
RESUMEN
Chemical investigation of an endophytic fungus Diaporthe foeniculina SCBG-15, led to the isolation of eight new cyclohexanone derivatives, foeniculins A-H (1-8) and three new phenolic acid derivatives, foeniculins I-K (9-11). Their structures were extensively established on the basis of 1H and 13C NMR spectra together with COSY, HSQC, HMBC, and NOESY experiments. The absolute configurations were confirmed by quantum chemical ECD calculations and single-crystal X-ray diffractions. Moreover, the in vitro cytotoxic and antibacterial activities of isolated compounds 1-11 were also evaluated.
RESUMEN
A chemical investigation on the EtOAc extract of the endophytic fungus Eutypella scoparia SCBG-8 led to the isolation of eight new sesquiterpenes eutyscoparins A-H (1-8), one C-28 steroid eutyscoparene A (9), one triterpenoid eutyscoparene B (10), six known terpenoids, and two known steroids. Their structures including absolute configurations were established on the basis of spectroscopic data analysis, single-crystal X-ray diffraction experiments, and electronic circular dichroism (ECD) calculations. Compound 7 displayed antibacterial activity against S. aureus and MRSA (methicillin-resistant Staphylococcus aureus) with MIC values of 6.3 µg/mL.
Asunto(s)
Antibacterianos/farmacología , Ascomicetos/química , Sesquiterpenos/farmacología , Esteroides/farmacología , Antibacterianos/aislamiento & purificación , Línea Celular Tumoral , China , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Hojas de la Planta/química , Sesquiterpenos/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Esteroides/aislamiento & purificación , Terpenos/aislamiento & purificaciónRESUMEN
The first concise total syntheses of sanctis A and B were reported, and it enabled revision of the structure of sanctis B through single-crystal X-ray diffraction. The established synthetic approach mainly mimics a biosynthetic olefin isomerization/hemiacetalization/dehydration/[3 + 3]-type cycloaddition cascade sequence, offering a viable synthetic methodology to efficiently access sanctis A-B and their analogues.