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This review highlights the key findings in the area of cancer therapy. Triazole derivatives possess anticancer activity against various human cancer cell lines, and hence the triazole core may act as a lead molecule for the synthesis of novel anticancer drugs.
This review highlights the key findings in the area of cancer therapy. Triazole derivatives possess anticancer activity against various human cancer cell lines, and hence the triazole core may act as a lead molecule for the synthesis of novel anticancer drugs.Proteolysis targeting chimeras (PROTACs) are an emerging class of targeted protein degraders that coopt the intracellular degradation machinery to selectively deplete their respective targets. PROTACs act as bifunctional degraders that comprise ubiquitin E3 ligase- and target-binding moieties connected by chemical linkers with appropriate physicochemical properties. Through this bivalent structure, PROTACs induce the degradation of their targets via proximity-based pharmacology. Compared to conventional inhibitors, PROTACs exhibit superior pharmacologic properties in terms of efficacy, potency, selectivity, the durability of response, and efficacy against undruggable proteins. Over the last few years, the scientific community has witnessed significant endeavors to advance this field and expand the armamentarium of PROTACs. In this perspective, we highlight these advances with an emphasis on emerging PROTAC variants, PROTACtability and degradability of protein targets, expression-guided PROTACs, multivalent PROTACs, preclinical resistance, candidates evaluated in clinical trials, and prospects for the use of PROTACs as a therapeutic modality.
Sargassum is a marine organism, it tends to increase its population drastically damaging the environment and risking other organisms, however sargassum could represent a source of bioactive compounds to treat different diseases such as cancer. Thus, aqueous, ethanolic, and ethyl acetate extracts of sargassum from Playa del Carmen Mexico were obtained to be subjected to metabolomic and antiproliferative assays in breast cancer cells.
To evaluate the effect of aqueous, ethanolic, and ethyl acetate extracts from Mexican sargassum in Artemia salina bioassays and its antiproliferative effects in MCF-7, MDA-MB-231 and NIH3T3 cell lines, finally by UHPLC-MS/MS to identify the metabolites in each extract and relate them with its antiproliferative effect.
The sargassum sample collection was carried out in September, in 3 different points of Playa del Carmen, Quintana Roo, Mexico. The aqueous, ethanolic and ethyl acetate extracts of Mexican sargassum were obtained by evaporation of solvent and lyophilization. Thefect observed be due to their metabolites which could be ligands for the sphingosine kinase 1 as was demonstrated by docking studies.
The ethanolic extract obtained from sargassum has better antiproliferative activity, despite not having cytotoxic effect in Artemia salina. The antiproliferative effect could be related with the sphinganine C16, N,N-Dimethylphingosine identified with more abundance by UHPLC-MS/MS. In addition, these metabolites could be target of sphingosine kinase 1.
The ethanolic extract obtained from sargassum has better antiproliferative activity, despite not having cytotoxic effect in Artemia salina. The antiproliferative effect could be related with the sphinganine C16, N,N-Dimethylphingosine identified with more abundance by UHPLC-MS/MS. In addition, these metabolites could be target of sphingosine kinase 1.In times of Covid19 epidemic/pandemic, cardiac patients are vulnerable group with many specific conditions that could aggravate their condition. In this narrative review, we present possible measures adequate in managing cardiac patients in epidemic outbreak. The overview on role of cardiologists and Crisis Management Team in management of cardiac patients is given. Protocols and measures implemented in Covid19 crises are presented in light of risk assessment and disease prevention of cardiac patients and measures that should be taken for each cardiac condition. Specificity of epidemics calls for specific measures in addressing cardiac patients as part of the affected population. Many possible outcomes could be expected in an epidemic outbreak in relation to cardiovascular diseases, but tailored measures will keep cardiac patients safe. Proposed preventive measures for cardiac patients could be implemented in existing protocols for epidemic outbreak.
Coronavirus disease 2019 (COVID 19) is a worldwide pandemic that has devastated the world in a way that has not been witnessed since the Spanish Flu in 1918. In this study, we aim to investigate the outcomes of patients with rheumatic diseases infected with COVID-19 in Oman.
A multi-center retrospective cohort study included patients with underlying rheumatological conditions and COVID-19 infection. Data were collected through the electronic record system and by interviewing the patients through a standard questionnaire.
113 patients with different rheumatic diseases were included with the following rheumatological diagnoses rheumatoid arthritis (40.7%), systemic lupus erythematosus (23.1%), psoriatic arthritis (8%), Behcet's disease (7%), ankylosing spondylitis (6.2%), other vasculitides, including Kawasaki disease (4.4%), and other diagnoses (10.6%). The mean (SD) age of patients was 43 (14) years, and 82.3% were female. The diagnosis of COVID-19 was confirmed by PCR test in 84.1% of the patients. Thegeneral population, with diabetes, morbid obesity, chronic kidney diseases, interstitial lung disease, cardiovascular disease, obstructive lung disease, and liver diseases as comorbidities being the most severe risk factors associated with death. Greater care should be provided to this population, including the prompt need for vaccination.
COVID-19 infection in patients with rheumatic diseases have an increased mortality rate in comparison to the general population, with diabetes, morbid obesity, chronic kidney diseases, interstitial lung disease, cardiovascular disease, obstructive lung disease, and liver diseases as comorbidities being the most severe risk factors associated with death. Greater care should be provided to this population, including the prompt need for vaccination.
A simple, transition-metal-free C-S coupling protocol for the synthesis of aryl thioethers is reported.
Sulfur-containing moieties are ubiquitous in pharmaceutical drugs and materials and therefore methods for their construction are of great importance. One approach entails the catalytic coupling of an aryl halohydrocarbon with a thiol, but the transition metal catalysts usually used are prone to poisoning by participating sulfur species and efficient catalysis is usually only achieved after complex ligand optimization.
New transition-metal-free approaches to the synthesis of C-S bonds are urgently need.
We screened the reaction conditions such as alkali, crown ether, solvent, temperature, etc., tested the compatibility of the reaction substrate, and analyzed the mechanism process.
The optimized reaction conditions were determined to be 1.0 equiv of aryl halides and 1.2 equiv of thiols at 110 ℃ in toluene with K2CO3 (1.5 equiv) as a base, promoted by 10 mol% dicyclohexano-18-crown-6. Up to 33 examples of thioethers were synthesized under transitionmetal- free conditions in good to excellent yields.
We have developed a simple and efficient method for the C-S cross-coupling of a wide variety of (hetero)aryl halides and thiols mediated by dicyclohexano-18-crown-6 and without the need for transition-metal catalyst. In addition, the preparation and gram-scale experiments of a variety of drug molecules further verify the practicability of our developed method.
We have developed a simple and efficient method for the C-S cross-coupling of a wide variety of (hetero)aryl halides and thiols mediated by dicyclohexano-18-crown-6 and without the need for transition-metal catalyst. In addition, the preparation and gram-scale experiments of a variety of drug molecules further verify the practicability of our developed method.
To explore angiopoietin-1 (Ang-1) involved in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) through effected on endoplasmic reticulum stress (ERS) and apoptosis of vascular endothelial cells (VECs).
CVS accounts for high morbidity and mortality of aSAH. Abnormal cellular physiological processes of VECs play a critical rale in aSAH induced CVS. In addition, Ang-1 involve in the regulation of vascular structure and function.
To study the role of Ang-1 played in CVS and the underlying mechanism.
Blood samples of 130 aSAH patients were collected from 2016 to 2020 in West China Hospital of Sichuan University. Two-hemorrhage rodent model was employed to structured aSAH-induced CVS rat model. And oxyHb was used to treat VECs to constructed CVS cell model in vitro. ELISA was used to measure the level of Ang-1. HE staining was used to assess basilar arteries of rat. CCK-8 was used to detect cell viability ability. Flow cytometry was used to test the cell apoptosis rate. Western blott p53 mediated ERS and apoptosis of VECs by activated PI3K/Akt pathway, Ang-1 might be an attractive treatment strategy for CVS.
Clarithromycin (antibiotic), due to its narrow absorption window in gastrointestinal tract, was taken as a model drug.
Focusing on the efficient drug delivery system, floating tablets that remain buoyant over gastric fluid for 24 hrs were produced by adopting the Melt Mold method using beeswax, gelucire, and oleic acid. To modulate the release pattern, a different concentration of 48/16 of beeswax and gelucire was used.
To evaluate and characterize the final product, several tests, including the percentage recovery, in-vitro release studies, clarithromycin loading, Scanning electron microscopy, Differential scanning calorimeter, X-ray power diffractometry, Fourier transform infrared spectroscopy, weight variation, hardness, and friability, were carried out. Regarding the results, the encapsulation efficiency of the floating tablets was 39.5% to 59%, having a weight variation with and without gelucire 48/16 0.09525±0.0032g, and 0.09527±0.00286g to 0.0957±0.00321g respectively. Clarithromycin release was controlled by using hydrophobic beeswax and hydrophilic gelucire 48/16. X-ray power diffractometry, differential scanning calorimeter, fourier transform infrared spectroscopy confirmed the absence of drug-polymer interaction, amorphous, and crystalline form of the drug after encapsulation. Drug release kinetics were determined by applying the different models such as zero-order, first-order model, hi-guchi, and Korsemeyer-Pappas model. All formulations follow the Korsmeyer-Peppas model at 1.2 pH.
Gastro retentive drug delivery systems were produced by using melt molding technique. In vitro dissolution represents sustained release of drug from formulation.
Gastro retentive drug delivery systems were produced by using melt molding technique. In vitro dissolution represents sustained release of drug from formulation.
Bone fracture healing is a time-consuming and high-priority orthopedic problem worldwide.
Discovering the potential mechanism of bone healing at a time course and transcriptional level may better help manage bone fracture.
In this study, we analyze a time-course bone fracture-healing transcriptional data set in a rat model (GSE592, GSE594, and GSE1371) of Gene Expression Omnibus (GEO). RNA was obtained from female Sprague-Dawley rats with femoral fracture at the initial time (day 3) as well as early (week 1), middle (week 2), and late (week 4) time periods, with nonfracture rats used as control. Gene Ontology (GO) functional analysis and pathway examinations were performed for further measurements of GSEA and hub genes.
Results indicated that the four stages of bone fracture healing at the initial, early, middle, and late time periods represent the phases of hematoma formation, callus formation, callus molding, and mature lamellar bone formation, respectively. SAR7334 molecular weight Extracellular organization was positively employed throughout the four stages.
