10/02/2024


The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.Hepatitis C virus (HCV) is a primary cause of chronic liver disease along with various complications like liver cirrhosis and malignancy which leads to death. It has infected more than 185 million people worldwide. There is no congruence established for the treatment of various genotypes of HCV infection owing to diversity in prevalence globally. https://www.selleckchem.com/products/dir-cy7-dic18.html Assessment of affected individuals with HCV by polymerase chain reaction (PCR), viral load of HCV and liver enzyme levels (i.e., ALT and AST) are the foundation to evaluate the safety and efficacy of HCV therapies. The antiviral efficacy has been greatly improved and sustained viral response (SVR) rates increased from 6% with interferon monotherapy to 50-80% with PEG-interferon/ribavirin combination therapy to >95% after the approval of all interferon free oral direct acting antiviral agents. The main objective of this review article is to compile data from reference sources regarding the old and current therapeutic strategies used to manage HCV infection. It is accepted that chronic HCV infection increases patient's thrombocytopenia and neutropenia risk and complications increased in co-morbid disorders like in tuberculosis, HIV, diabetes etc. In past treatment associated side effects were the major consequences and many patients have to stop the treatment. But after the approval of direct acting antiviral drugs create a revolution in the treatment of HCV infection. So, it could be concluded that current combination therapies are a promising hope to eradicate and to control HCV but some safety concerns required more considerations Therefore, this review focus on the available latest combination therapies and their effectiveness to eradicate HCV infection.In the presented work, 2,3-dihydro-1,4-benzodioxin-6-amine (1) was reacted with 4-chlorobenzenesulfonyl chloride (2) in presence of aqueous basic aqueous medium to obtain 4-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-yl)benzenesulfonamide (3). In parallel, various un/substituted anilines (4a-l) were treated with bromoacetyl bromide (5) in basified aqueous medium to obtain corresponding 2-bromo-N-(un/substituted)phenylacetamides (6a-l) as electrophiles. Then the compound 3 was finally reacted with these electrophiles, 6a-l, in dimethylformamide (DMF) as solvent and lithium hydride as base and activator to synthesize a variety of 2-[[(4-chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(un/substituted)phenylacetamides (7a-l). The synthesized compounds were corroborated by IR, 1H-NMR and EI-MS spectral data for structural confirmations. These molecules were then evaluated for their antimicrobial and antifungal activities along with their %age hemolytic activity. Some compounds were found to have suitable antibacterial and antifungal potential, especially the compound 2-[[(4-chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(3,5-dimethylphenyl)acetamide (7l) exhibited good antimicrobial potential with low value of % hemolytic activity.The present study aimed to assess the effects of 3,4-dihydroxyacetophenone (DHAP) on human pulmonary artery smooth muscle cells (HPASMCs). HPASMCs were divided into the normoxia group (NG), hypoxia group (HG), and hypoxia and 0.6×10-4 mol/L (HD1), 1.9×10-4 mol/L (HD2) and 6.0×10--4 mol/L (HD3) DHAP treatment groups. Cell cycle was analyzed by flow-cytometrically. HPASMC growth was examined by the proliferating cell nuclear antigen (PCNA) and MTT assays. Intracellular Ca2+ ([Ca2+]i) was measured by laser scanning confocal microscopy. Compared with the NG, the HG showed significantly increased HPASMC proliferation (P less then 0.05); meanwhile, cells treated with DHAP showed decreased proliferation compared with the HG (P less then 0.05). Hypoxia enhanced cell cycle progression and DHAP partly restored cell cycle distribution toward the status of NG cells. Furthermore, CDK2 levels were markedly increased in hypoxic cells (P less then 0.05), while DHAP treatment starkly decreased CDK2 levels in comparison with the HG (P less then 0.05). Moreover, hypoxia increased intracellular [Ca2+] levels compared with normoxia (P less then 0.05); meanwhile, DHAP treatment decreased [Ca2+]i compared with the HG (P less then 0.05). These findings suggested that DHAP inhibits hypoxia-induced proliferation of HPASMCs involving [Ca2+]i reduction. Therefore, DHAP should be considered an ideal candidate for the prevention and/or treatment of hypoxia-associated pulmonary hypertension and pulmonary vascular remodeling.The objective of this study is to mask the extremely bitter taste of tilmicosin, and the tilmicosin-resin complex (DRC) microsphere were prepared by entrapping tilmicosin into resins (Tulsion® 339 and Eudragit® RS/ RL 100) for further pharmacokinetics study in rat. The DRC was characterized by FTIR and X-ray diffraction, and the microsphere containing DRC and Eudragit® RS/RL 100 were characterized by scanning electron microscopy (SEM). The rats were orally administrated with tilmicosin phosphate (10 mg/kg) and the microsphere containing the same dose of tilmicosin, respectively. These microspheres do not taste bitter and the kinetics study suggests that the drug released from microsphere meet the first order kinetics (r = 0.9911). The experimental results showed that T½ and Tmax of microsphere were much longer than tilmicosin phosphate, which indicates that the oral microsphere can be a promising long-active formulation for taste masking of tilmicosin.The hepatoprotective effects of a water extract formula (WEF) derived from three selected TCM herbs (i.e. Corn silk (Maydis stigma), lotus leaf (Nelumbo nucifera Gaertn) and dandelion (Taraxacum officinale)) were apprised by the antioxidant activities and by the decay of carbon tetrachloride (CCl4)-induced rats. The results indicated that the WEF had higher contents of total phenolic and flavonoids, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging ability, ferric reducing antioxidant potential (FRAP) and equivalent antioxidant capacity (TEAC). The animal experiments revealed that the WEF administration could lower malondialdehyded (MDA) level, serum alanine aminotransferase (ALT), aspartate amino transferase (AST) activities, resume triglyceride (TG) and decreased glutathione (GSH) levels, and reform or resume super oxide dismutase (SOD) content as well as improve peroxidase (GPx), glutathione reductase (GRd) and catalase (CAT) activities in CCl4-induced rats. The histological inspections of liver demonstrated that CCl4 enlarged the extents of bile duct proliferation, necrosis, fibrosis, steatosis and fatty vacuolation all round liver, but the first three can be ameliorated by WEF.