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1.
Front Pharmacol ; 12: 649398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335241

RESUMO

Long non-coding RNA (lncRNA) is widely reported to be involved in cardiac (patho)physiology. Acute myocardial infarction, in which cardiomyocyte apoptosis plays an important role, is a life-threatening disease. Here, we report the lncRNA Chaer that is anti-apoptotic in cardiomyocytes during Acute myocardial infarction. Importantly, lncRNA Chaer is significantly downregulated in both oxygen-glucose deprivation (oxygen-glucose deprivation)-treated cardiomyocytes in vitro and AMI heart. In vitro, overexpression of lncRNA Chaer with adeno virus reduces cardiomyocyte apoptosis induced by OGD-treated while silencing of lncRNA Chaer increases cardiomyocyte apoptosis instead. In vivo, forced expression of lncRNA Chaer with AAV9 attenuates cardiac apoptosis, reduces infarction area and improves mice heart function in AMI. Interestingly, overexpression of lncRNA Chaer promotes the phosphorylation of AMPK, and AMPK inhibitor Compound C reverses the overexpression of lncRNA Chaer effect of reducing cardiomyocyte apoptosis under OGD-treatment. In summary, we identify the novel ability of lncRNA Chaer in regulating cardiomyocyte apoptosis by promoting phosphorylation of AMPK in AMI.

2.
Nat Commun ; 12(1): 3272, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075051

RESUMO

Organic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.

3.
Chemistry ; 27(4): 1297-1300, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-32966636

RESUMO

A hydrogen bond donor solvent assisted (radio)halogenation and deuteration of organoborons has been developed. The reactions exhibited high functional group tolerance and needed only an ambient atmosphere. Most importantly, compared to literature methods, our conditions are more consistent with the principals of green chemistry (e.g., metal-free, strong oxidant-free, more straightforward conditions).

4.
Ultrasonics ; 110: 106272, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33065465

RESUMO

Sonodynamic therapy (SDT) is a promising modality for cancer treatment. Sinoporphyrin sodium (DVDMS), purified from Photofrin II, shows great potential in SDT evidenced by growing studies. The purpose of the current study was to investigate the antitumor effect of SDT combined with DVDMS on human glioblastoma (U87 MG) cell line in vitro. The cellular uptake of DVDMS was investigated by confocal microscopy and IVIS spectrum imaging system. In addition, DVDMS toxicity and anti-tumor effect of SDT were assessed by flow cytometry. The generation of intracellular reactive oxygen species (ROS) was determined using DCFH-DA staining. Simultaneously, fluorescence microscopy was performed to access the destabilization of mitochondrial membrane potential (MMP). The results showed that DVDMS could easily enter the cells and accumulated in the cytoplasm, especially the mitochondria. And the intracellular DVDMS increased with incubation time or concentrations. The results also showed remarkable cytotoxicity of DVDMS-mediated SDT (center frequency: 0.970 MHz; peak-rarefactional pressure: 0.52-MPa; acoustic power: 0.32 W; pulse repetition frequency: 1 Hz; duty cycle: 1-30%; duration: 3 min) on U87 MG cells, while DVDMS alone was non-toxic to the cells. In comparison with the control group, the SDT-treated group showed significant generation of intracellular ROS and loss of MMP at 1 h post-treatment. These results indicated that DVDMS-mediated SDT could induce great cytotoxicity in U87 MG cells via the production of ROS and showed potentials in the treatment for glioblastoma.


Assuntos
Antineoplásicos/farmacologia , Glioblastoma/terapia , Porfirinas/farmacologia , Terapia por Ultrassom/métodos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Equipamento , Humanos , Técnicas In Vitro , Potencial da Membrana Mitocondrial , Necrose , Espécies Reativas de Oxigênio/metabolismo
5.
Ann Palliat Med ; 9(6): 4252-4261, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33183055

RESUMO

Recent studies have demonstrated the limitations of the CHA2DS2-VASc score [congestive heart failure, hypertension, age (>65 years =1 point; >75 years =2 points), diabetes, and previous stroke/ transient ischemic attack (2 points), vascular disease] which lacks many of less common risk factors for stroke. Moreover, only two risk factors, gender and age, are assigned with different points according to the stratification in the CHA2DS2-VASc score. Thus, this meta-analysis was aimed to optimize the stratification of risk factors in and beyond the CHA2DS2-VASc score for patients in mainland China. PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Journal Database (VIP) were searched from their inception to January 2020 for articles assessing risk factors of nonvalvular atrial fibrillation (NVAF) with ischemic stroke in mainland China. Odd risks (ORs) with 95% confidence intervals (CIs) were applied for dichotomous variable, and the weighed mean differences (WMDs) with standard deviations (SDs) were used for continuous variables. The meta-analysis included 20 eligible studies involving 14,675 patients. Compared with the non-stroke group [systolic blood pressure (SBP): 132.99 mmHg, 95% CI: 131.86-134.12; diastolic blood pressure (DBP): 80.08 mmHg, 95% CI: 78.63-81.53], the ischemic stroke group (SBP:144.07 mmHg, 95% CI: 140.74- 147.40; DBP: 84.41 mmHg, 95% CI: 82.39-86.43) showed increased levels of SBP (WMD 10.98 mmHg, 95% CI: 7.80-14.17, P<0.00001) and DBP (WMD 4.46 mmHg, 95% CI: 2.57-6.35, P<0.00001). In addition, the ischemic stroke group demonstrated significantly lower levels of left ventricular ejection fractions (LVEFs) (WMD 3.05% 95% CI: -5.96 to -0.14, P=0.04), and significantly higher levels of total cholesterol (TC) (WMD 0.32 mmol/L, 95% CI: 0.04-0.61, P=0.02) and low density lipoprotein cholesterol (LDL-C) (WMD 0.14 mmol/L, 95% CI: 0.02-0.26, P=0.02), as compared with the non-stroke group. The optimized stratification and the addition of risk factors in and beyond the CHA2DS2-VASc score may improve the predictive performance, thus helping to differentiate patients with the real thromboembolic risk.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia , Idoso , China , Humanos , Medição de Risco , Fatores de Risco
6.
Front Oncol ; 10: 1008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903590

RESUMO

Cancer, especially malignant tumors with poor prognosis, has become a major hazard to human life and health. The tumor microenvironment is gaining increasing attention from researchers, as it offers a new focus for tumor diagnosis, therapy, and prognosis. The numbers of immune and stromal cells, which are major components of the tumor microenvironment, could be determined from RNA-seq data with the Estimation of STromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) algorithm. To explore the effects of immune and stromal cells on tumor prognosis, we analyzed associations between overall survival and immune/stromal scores for 20 malignant tumor types based on The Cancer Genome Atlas (TCGA) data. For six of the 20 tumor types, we observed statistically significant associations. Furthermore, to better explain the predictive ability of these scores, differentially expressed genes (DEGs) were identified in groups of cases with high or low immune or stromal scores for each of these six malignant tumor types. In addition, a list of immune-related genes was screened to identify prognostic predictors for one or more tumor types. Thus, multi-database joint analysis can provide a new approach to the assessment of tumor prognosis and allow the identification of related genes that may be new biomarkers for tumor metastasis and prognosis.

7.
J Orthop Surg Res ; 15(1): 302, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762763

RESUMO

OBJECTIVE: There is no consensus on the best choice between high- and low-viscosity bone cement for percutaneous vertebroplasty (PVP). This study aimed to compare the clinical and radiological outcomes and leakage between three cements with different viscosities in treating osteoporotic vertebral compression fractures. METHODS: This is a prospective study comparing patients who were treated with PVP under local anesthesia: group A (n = 99, 107 vertebrae) with high-viscosity OSTEOPAL V cement, group B (n = 79, 100 vertebrae) with low-viscosity OSTEOPAL V cement, and group C (n = 88, 102 vertebrae) with low-viscosity Eurofix VTP cement. Postoperative pain severity was evaluated using the visual analog scale. Cement leakage was evaluated using radiography and computed tomography. RESULTS: There was no significant difference in the incidence of cement leakage between the three groups (group A 20.6%, group B 24.2%, group C 20.6%, P = 0.767). All three groups showed significant reduction in postoperative pain scores but did not differ significantly in pain scores at postoperative 2 days (group A 2.01 ± 0.62, group B 2.15 ± 0.33, group C 1.92 ± 0.71, P = 0.646). During the 6 months after cement implantation, significantly less reduction in the fractured vertebral body height was noticed in group B and group C than in group A (group A 19.0%, group B 8.1%, group C 7.3%, P = 0.009). CONCLUSIONS: Low-viscosity cement has comparable incidence of leakage compared to high-viscosity cement in PVP for osteoporotic vertebral compression fractures. It also can better prevent postoperative loss of fractured vertebral body's height.


Assuntos
Cimentos Ósseos/química , Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos/uso terapêutico , Estudos de Casos e Controles , Cementoplastia/métodos , Feminino , Fraturas por Compressão/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico , Dor Pós-Operatória/epidemiologia , Polimetil Metacrilato/química , Polimetil Metacrilato/uso terapêutico , Estudos Prospectivos , Radiografia/métodos , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Viscosidade , Escala Visual Analógica
8.
Chem ; 6(4): 1018-1031, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32685767

RESUMO

We describe a catalyst-free 1,2-trans-dihalogenation of alkynes with an unprecedented substrate scope and exclusive regio- and stereoselectivity. This versatile dihalogenation system-a combination of NX1S electrophile and alkali metal halide (MX2) in acetic acid-is applicable for diverse categories of alkynes (electron-rich or poor alkynes, internal and terminal alkynes, or heteroatoms such as O-, N-, S-substituted alkynes). The hydrogen bonding donor solvent acetic acid is essential for the in-situ generation of X1X2 electrophile, including ICl, IBr, BrCl, I2, and Br2.

9.
Angew Chem Int Ed Engl ; 59(38): 16398-16403, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32495485

RESUMO

The difluoromethyl group (CF2 H) is considered to be a lipophilic and metabolically stable bioisostere of an amino (NH2 ) group. Therefore, methods that can rapidly convert an NH2 group into a CF2 H group would be of great value to medicinal chemistry. We report herein an efficient Cu-catalyzed approach for the conversion of alkyl pyridinium salts, which can be readily synthesized from the corresponding alkyl amines, to their alkyl difluoromethane analogues. This method tolerates a broad range of functional groups and can be applied to the late-stage modification of complex amino-containing pharmaceuticals.

10.
Biomed Eng Online ; 19(1): 52, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552718

RESUMO

BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Sonodynamic therapy (SDT) is an emerging cancer therapy, and in contrast to photodynamic therapy, could non-invasively reach deep-seated tissues and locally activates a sonosensitizer preferentially accumulated in the tumor area to produce cytotoxicity effects. In comparison with traditional treatments, SDT may serve as an alternative strategy for human colon cancer treatment. Here, we investigated the sonodynamic effect using sinoporphyrin sodium (DVDMS) as a novel sonosensitizer on human colon cancer cells in vitro. RESULTS: The absorption spectra of DVDMS revealed maximum absorption at 363 nm wavelength and emission peak at 635 nm. Confocal microscopy images revealed the DVDMS was primarily localized in the cytoplasm, while no evident signal was detected within the nuclei. Flow cytometry analysis showed rapid intracellular uptake of DVDMS by two types of human colon cancer cells (HCT116 and RKO). Cell viability of HCT116 was tolerant with the concentration of DVDMS up to 20 µg/mL, while the case of RKO was 5 µg/mL. In comparison with the control group, the SDT-treated groups of these two types of human colon cancer cells showed significant increase in cellular apoptosis and necrosis ratio. Increased intracellular reactive oxygen species (ROS) production was detected, indicating the involvement of ROS in mediating SDT effects. CONCLUSION: DVDMS results an effective sonosensitizer for the ultrasound-mediated cancer cell killing, and its anticancer effect seems to rely on its ability to produce ROS under ultrasound exposure.


Assuntos
Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Porfirinas/farmacologia , Terapia por Ultrassom/métodos , Apoptose/efeitos dos fármacos , Transporte Biológico , Células HCT116 , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Necrose/induzido quimicamente , Porfirinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
ACS Sens ; 5(8): 2359-2366, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32388982

RESUMO

Circulating tumor cells (CTCs) have been utilized in the diagnosis and prognosis of tumor. However, the CTC concentration is extremely low to be detected in peripheral blood. Many existing methods suffer from either expensive labeling or complex operation. In this study, we constructed a label- and enzyme-free and sensitive method to detect the breast cancer CTCs. First of all, a probe containing a breast cancer cell-specific aptamer and a complementary single-stranded DNA (trigger DNA P1) were designed. When the target cells are present, the aptamer binds to the CTCs and releases P1 which triggers the strand displacement amplification. This process generates three-way junction structure DNA, the specific translocation signals of which are identified by nanopore assay. The detection limit of tumor cells is 5 in the current experimental setup and can be further reduced. Furthermore, the method is demonstrated in a clinical sample test with high recovery rate and accuracy. Our results suggest that this method could be applied to early diagnosis of metastatic recurrence and prognosis determination.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama , Nanoporos , Células Neoplásicas Circulantes , Neoplasias da Mama/diagnóstico , Contagem de Células , Humanos
12.
Adv Exp Med Biol ; 1229: 215-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285414

RESUMO

Heart failure (HF) is a leading cause of death worldwide and is still growing. Thus, it's critical to understand the molecular causes of HF and develop effecitive therapies to treat HF. Recently, scientists and clinicians identified that noncoding RNAs play important roles in pathogenesis of HF. Some of noncoding RNAs can serve as novel biomarkers for HF and some of them contribute to the progression of HF. In addition, noncoding RNAs can be related to well-known HF risk factors, such as hypertension, diabetes etc. In this review, we sought to summarize current knowledge about noncoding RNAs and noncoding RNAs mediated regulation of HF and its risk factors.


Assuntos
Insuficiência Cardíaca , RNA não Traduzido , Biomarcadores , Humanos , Hipertensão
13.
J Cardiovasc Pharmacol ; 75(5): 446-454, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32141990

RESUMO

Atherosclerosis (AS), known as the chronic inflammatory disease, results from the dysfunction of vascular endothelial cells (VECs). Transforming growth factor-ß1 (TGF-ß1) has been reported to be induced by oxidized low-density lipoprotein (ox-LDL) and contribute to AS-related vascular endothelial cell damage. This work planned to study the mechanism of TGF-ß1 in vascular endothelial cell damage. We found that TGF-ß1 was activated by ox-LDL in human umbilical vascular endothelial cells (HUVECs). Silence of TGF-ß1 reversed the inductive effect of ox-LDL on apoptosis and inflammatory response of HUVECs. Mechanistically, microRNA-4286 (miR-4286) targeted and inhibited TGF-ß1 to inhibit Smad3, and Smad3 bound to the promoter of miR-4286 to repress its transcription. Rescue assays indicated that miR-4286 ameliorated the ox-LDL-induced apoptosis and inflammatory response through inhibiting TGF-ß1. In conclusion, our study first demonstrated that miR-4286/TGF-ß1/Smad3-negative feedback loop ameliorated vascular endothelial cell damage by attenuating apoptosis and inflammatory response, providing new thoughts for promoting the treatment of AS.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lipoproteínas LDL/toxicidade , MicroRNAs/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células Cultivadas , Retroalimentação Fisiológica , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , MicroRNAs/genética , Transdução de Sinais , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética
14.
IEEE Trans Cybern ; 50(8): 3444-3457, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31034428

RESUMO

One of the most important and widely faced optimization problems in real applications is the interval multiobjective optimization problems (IMOPs). The state-of-the-art evolutionary algorithms (EAs) for IMOPs (IMOEAs) need a great deal of objective function evaluations to find a final Pareto front with good convergence and even distribution. Further, the final Pareto front is of great uncertainty. In this paper, we incorporate several local searches into an existing IMOEA, and propose a memetic algorithm (MA) to tackle IMOPs. At the start, the existing IMOEA is utilized to explore the entire decision space; then, the increment of the hypervolume is employed to develop an activation strategy for every local search procedure; finally, the local search procedure is conducted by constituting its initial population, whose center is an individual with a small uncertainty and a big contribution to the hypervolume, taking the contribution of an individual to the hypervolume as its fitness function, and performing the conventional genetic operators. The proposed MA is empirically evaluated on ten benchmark IMOPs as well as an uncertain solar desalination optimization problem and compared with three state-of-the-art algorithms with no local search procedure. The experimental results demonstrate the applicability and effectiveness of the proposed MA.

15.
Front Pharmacol ; 11: 585680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33390954

RESUMO

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown. Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function. Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-ß1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-ß1 dependent. Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis.

16.
Nat Commun ; 10(1): 5083, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704937

RESUMO

Nanoscale transport through nanopores and live-cell membranes plays a vital role in both key biological processes as well as biosensing and DNA sequencing. Active translocation of DNA through these nanopores usually needs enzyme assistance. Here we present a nanopore derived from truncated helicase E1 of bovine papillomavirus (BPV) with a lumen diameter of c.a. 1.3 nm. Cryogenic electron microscopy (cryo-EM) imaging and single channel recording confirm its insertion into planar lipid bilayer (BLM). The helicase nanopore in BLM allows the passive single-stranded DNA (ssDNA) transport and retains the helicase activity in vitro. Furthermore, we incorporate this helicase nanopore into the live cell membrane of HEK293T cells, and monitor the ssDNA delivery into the cell real-time at single molecule level. This type of nanopore is expected to provide an interesting tool to study the biophysics of biomotors in vitro, with potential applications in biosensing, drug delivery and real-time single cell analysis.


Assuntos
DNA Helicases/metabolismo , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/metabolismo , Bicamadas Lipídicas/metabolismo , Nanoporos/ultraestrutura , Proteínas Virais/metabolismo , Microscopia Crioeletrônica , DNA Helicases/ultraestrutura , Proteínas de Ligação a DNA/ultraestrutura , Células HEK293 , Humanos , Microscopia Confocal , Técnicas de Patch-Clamp , Transfecção , Proteínas Virais/ultraestrutura
17.
J Am Chem Soc ; 141(50): 19941-19949, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31756095

RESUMO

We report herein the first catalytic strategy to harness amidyl radicals derived from N-chloroamides for C-C bond formation, allowing for the discovery of the first catalytic benzylic C-H difluoromethylation. Under copper-catalyzed conditions, a wide variety of N-chlorocarboxamides and N-chlorocarbamates direct selective benzylic C-H difluoromethylation with a nucleophilic difluoromethyl source at room temperature. This scalable protocol exhibits a broad substrate scope and functional group tolerance, enabling late-stage difluoromethylation of bioactive molecules. This copper-catalyzed, chloroamide-directed strategy has also been extended to benzylic C-H pentafluoroethylation and trifluoromethylation. Mechanistic studies on the difluoromethylation reactions support that the reactions involve the formation of benzylic radicals via intramolecular C-H activation, followed by the copper-mediated transfer of difluoromethyl groups to the benzylic radicals.

18.
J Org Chem ; 84(17): 11240-11246, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31385517

RESUMO

A facile synthesis of Z-enamides via heterogeneous Au/TiO2 catalyzed stereoselective hydrogenation of ynamides has been developed. Easy to handle and inexpensive ammonium formate was used as the hydrogen source, and Z-enamides were formed in a highly stereoselective manner. The commercially available gold nanoparticle catalyst could be recycled multiple times without a significant loss of activity.

19.
Biomed Opt Express ; 10(8): 4290-4304, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31453011

RESUMO

Co-amorphous drugs have shown significant potential in improving the stability and bioavailability compared with single neat amorphous drugs. Here, we explored the molecular interactions of cimetidine, naproxen, indomethacin and their binary co-amorphous mixtures via Raman and terahertz (THz) spectroscopy. We used quench-cooled method to prepare the neat amorphous drugs and their binary co-amorphous mixtures and tested their thermodynamic properties through differential scanning calorimetry (DSC). Then, we found that the stability of co-amorphous drugs was stronger than their neat amorphous components. Furthermore, Raman spectroscopy was used to characterize the vibrational modes between different co-amorphous drugs. Generally, we found that the stability of co-amorphous drugs was better than their neat amorphous components for these samples we tested. Meanwhile, we complemented the detection of THz spectroscopy and found that crystalline and amorphous drugs could be better distinguished.

20.
J Am Chem Soc ; 141(29): 11398-11403, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31282666

RESUMO

We report herein a highly efficient Cu-catalyzed protocol for the conversion of aliphatic carboxylic acids to the corresponding difluoromethylated analogues. This robust, operationally simple and scalable protocol tolerates a variety of functional groups and can convert a diverse array of acid-containing complex molecules to the alkyl-CF2H products. Mechanistic studies support the involvement of alkyl radicals.

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