Synthesis and anti-inflammatory and analgesic activity of 5-(1H-benzo[d] imidazol-2-yl) methyl)-3-(3,5-dimethyl-4-isoxazolyl)-2-aryl-thiazolidin-4-ones

A new series of 5-(1H-benzo[d] imidazol-2-yl) methyl)-3-(3,5-dimethyl-4-isoxazolyl)-2-aryl-thiazolidin-4-ones 4 have been accomplished by a simple synthetic protocol. The reaction of 4-benzalamino-3,5-dimethylisoxazoles 3 with mercapto succinic acid furnishes 2-(3-(3,5-dimethyl-4-isoxazolyl)-4-oxo-2-aryl thiazolidin-5-yl) acetic acids 3, which are then cyclized to the title compounds viz., isoxazolyl thiazolyl benzimidazoles 4 on treatment with 1,2-phenylene diamines. The title compounds 4 have been screened for their anti-inflammatory and analgesic activity

NANOSPONGES: A REVIEW

The recent advance in nanotechnology has lead to the development of targeted drug delivery system. However, targeting a molecule to a particular site using a drug delivery system effectively requires a specialized drug delivery system. The discovery of nanosponge has become a significant step in overcoming certain problems such as drug toxicity, poor bioavailability and release of drug in a predictable fashion as they can accommodate both hydrophilic and hydrophobic drug. Nanosponges exhibit a porous structure in nature which has the unique ability to entrap the drug moieties and offers a merit of desire release. Nanosponges are tiny sponges that can circulate in the body to reach the specific site and binds on the surface to release the drug in a controlled and predictable manner. Nanosponges can be formulated by crosslinking of cyclodextrine with carbonyl or di-carboxylate (Crosslinkers). Nano sponge's technology has been explored widely for the delivery of drugs for oral administration, topical administration, and parental administration. Nanosponges can also serve as an effective carrier for enzyme, proteins, vaccine and antibodies. The present review highlights the method of preparation, characterization and their potential application in drug delivery system

CO-AMORPHOUS FORM OF (3S,4R)-3-ETHYL-4-(3H-IMIDAZO[1,2-A] PYRROLO[2,3-E] PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL) PYRROLIDINE-1-CARBOXAMIDE AND PROCESS FOR ITS PREPARATION THEREOF

Abstract The present invention pertains to co-amorphous form of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide of formula (I) and process for its preparation thereof. The chemical structure of compound of formula (I) is shown below

Co-infection with Influenza A and COVID-19

COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection

Photosensitizer Drug Delivery via an Optical Fiber

: An optical fiber has been developed with a maneuverable miniprobe tip that sparges O2 gas and photodetaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. The 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d8 (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control

Solid-State Hydrogen-deuterium Exchange Mass Spectrometry of Lyophilized Peptides

Proteins are susceptible to physical and chemical degradation in solution, which can lead to the loss of therapeutic activity and increase the potential for immunogenic responses when administered. Many degradation reactions are mediated by water, and therefore the proteins are often formulated as solids in which degradation rates are slowed significantly. Lyophilization is the most common method for producing solid protein formulations, which removes the water by sublimation and desorption under vacuum from the frozen protein solutions. Lyophilization requires excipients to protect the protein from the inherent stresses involved in the process. Degradation can still occur during lyophilization and storage, and needs to be characterized in order to develop a successful formulation with desired storage stability. The analytical techniques to characterize solid-state proteins are limited, however, and many do not provide site-specific information and lack the ability to predict stability beforehand. Recently, solid-state hydrogen-deuterium exchange mass spectrometry (ssHDX-MS) has been developed to characterize proteins in solid powders with peptide level resolution. The technique was found to be sensitive to formulation and process changes. The ssHDX-MS metrics are highly correlated to the long-term storage stability, suggesting that the method can serve as a formulation screening tool. This dissertation aims to evaluate the factors affecting ssHDX kinetics and to develop a mechanistic understanding of the exchange process in solid samples, which in turn will support the solid-state protein development and enable it to be conducted in a more a cost and time-effective way. First, the contribution of peptide-matrix interactions to deuterium incorporation kinetics in the absence of higher-order structure was assessed using lyophilized polyD, L-alanine peptides. Deuterium incorporation depended on excipient type and D2O(g) activity in the solid samples. A reversible pseudo-first-order kinetic model was proposed and validated using the experimental data. Second, the reversibility of the hydrogen-deuterium exchange reaction in the solid-state was evaluated to support the ssHDX mechanistic model further. The reaction was found to be reversible irrespective of initial conditions and independent of the excipient type. Prehydration of the peptide samples prior to deuterium labeling did not affect deuterium incorporation in amorphous samples compared to the controls not subjected to pre-hydration. Third, the contribution of peptide secondary structure to deuterium uptake kinetics was quantified using structured PDLA analogs. The deuterium incorporation in structured peptides was less than that of the PDLA peptides suggesting that both peptide structure and peptide-matrix interactions contribute to ssHDX-MS. Finally, a quantitative data analysis method was presented that allows the interpretation of ssHDX-MS data of a protein relative to controls. Altogether, the findings present a comprehensive mechanistic understanding of the ssHDX-MS of proteins that is relevant to the industry

Myopia progression varies with age and severity of myopia.

ObjectiveTo investigate annual myopia progression in individuals from South Indian states across different age groups, and its association with age of onset and severity of myopia.MethodsThis retrospective study included the data of 6984 myopes (range: 1-30 years), who visited at least twice to LV Prasad Eye Institute and on whom a standard retinoscopy technique was performed to determine refractive error. Based on spherical equivalent (SE) refractive error, individuals were classified into mild, moderate, high and severe myopic groups. Myopia progression was calculated as difference between SE at 1-year follow-up visit and at baseline. To determine the age-specific myopia progression, individuals were further categorized as myopes who are at least 15 years or younger and those who are above 15.ResultsThe mean annual progression of myopia was influenced by both the age group (p 15 years (-0.45 ± 0.01 vs. 0.14 ± 0.01, p 15 years, p = 0.71). Early onset of myopia was associated with high myopia in adulthood.ConclusionThe magnitude of myopia progression in children from South Indian states is comparable to that of Caucasians and Chinese. The greater progression in 'severe myopes' across different age groups emphasize the need for regular follow-ups, monitoring axial lengths, and anti-myopia strategies to control myopia progression irrespective of the age and degree of myopia