Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents.

The multifaceted nature of Alzheimer's disease (AD) demands treatment with multitarget-directed ligands (MTDLs) to confront the key pathological aberrations. A novel series of triazinoindole derivatives were designed and synthesized. In vitro studies revealed that all the compounds showed moderate to good anticholinesterase activity; the most active compound 23e showed an IC50 value of 0.56 ± 0.02 µM for AChE and an IC50 value of 1.17 ± 0.09 µM for BuChE. These derivatives are also endowed with potent antioxidant activity. To understand the plausible binding mode of the compound 23e, molecular docking studies and molecular dynamics simulation studies were performed, and the results indicated significant interactions of 23e within the active sites of AChE as well as BuChE. Compound 23e successfully diminished H2O2-induced oxidative stress in SH-SY5Y cells and displayed excellent neuroprotective activity against H2O2 as well as Aß-induced toxicity in SH-SY5Y cells in a concentration dependent manner. Furthermore, it did not show any significant toxicity in neuronal SH-SY5Y cells in the cytotoxicity assay. Compound 23e did not show any acute toxicity in rats at doses up to 2000 mg/kg, and it significantly reversed scopolamine-induced memory deficit in mice model. Additionally, compound 23e showed notable in silico ADMET properties. Taken collectively, these findings project compound 23e as a potential balanced MTDL in the evolution process of novel anti-AD drugs.

Critical Comparison of Structured Contactors for Adsorption-Based Gas Separations.

Recent advances in adsorptive gas separations have focused on the development of porous materials with high operating capacity and selectivity, useful parameters that provide early guidance during the development of new materials. Although this material-focused work is necessary to advance the state of the art in adsorption science and engineering, a substantial problem remains: how to integrate these materials into a fixed bed to efficiently utilize the separation. Structured sorbent contactors can help manage kinetic and engineering factors associated with the separation, including pressure drop, sorption enthalpy effects, and external heat integration (for temperature swing adsorption, or TSA). In this review, we discuss monoliths and fiber sorbents as the two main classes of structured sorbent contactors; recent developments in their manufacture; advantages and disadvantages of each structure relative to each other and to pellet packed beds; recent developments in system modeling; and finally, critical needs in this area of research.

Kikuchi-Fujimoto's Disease: Clinicopathological Correlation.

Kikuchi-Fujimoto's disease is a benign, self-limiting disorder characterized by regional tender lymphadenopathy fever and night sweats. It most commonly affects Asian adult females younger than 40 years of age. We report a case of 26 year female who presented with cervical lymphadenopathy, which on FNAC revealed Necrotizing Granulomatous inflammation which was unresponsive for three months of antitubercular therapy. A diagnosis of Kikuchi Fujimoto's disease was suggested on review of the slides at our institute and a biopsy confirmed the diagnosis.

Discovery of isoalloxazine derivatives as a new class of potential anti-Alzheimer agents and their synthesis.

This article describes discovery of a novel and new class of cholinesterase inhibitors as potential therapeutics for Alzheimer's disease. A series of novel isoalloxazine derivatives were synthesized and biologically evaluated for their potential inhibitory outcome for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds exhibited high activity against both the enzymes AChE as well as BuChE. Of the synthesized compounds, the most potent isoalloxazine derivatives (7m and 7q) showed IC50 values of 4.72 µM and 5.22 µM respectively against AChE; and, 6.98 µM and 5.29 µM respectively against BuChE. These two compounds were further evaluated for their anti-aggregatory activity for ß-amyloid (Aß) in presence and absence of AChE by performing Thioflavin-T (ThT) assay and Congo red (CR) binding assay. In order to evaluate cytotoxic profile of these two potential compounds, cell viability assay of SH-SY5Y human neuroblastoma cells was performed. Further, to understand the binding behavior of these two compounds with AChE and BuChE enzymes, docking studies have been reported.