Selection of Efficient Inhibitors for Caspas-9 according to Structure-Based Pharmacophore Screening Strategy and Molecular Dynamics Simulations

Caspases are enzymes which are the main pathways for apoptosis. Any irregulation in their functions causes increase or decrease in cell death, which result in autoimmune disease or cancer, respectively. In this study, structure-based pharmacophore drug discovery method as a virtual screening was used to discover selective inhibitors for caspase-9. This enzyme is an initiator caspase that is the main pathway in Alzheimer’s disease. A pharmacophore model was developed by investigating essential interactions among the reported potent inhibitors employing a docking analysis methodology. Applying pharmacophore virtual screening, nine compounds from both National Cancer Institute (NCI), and ZINC databases were filtered as potent inhibitors of caspase-9. The efficiency of the discovered compounds was further investigated by docking studies.HIGHLIGHTS•Caspase-9 is an important enzyme for apoptosis and its activity is pivotal in cell death.•A computational design of small molecular inhibitors for caspase-9 performed by structure-based pharmacophore model.•9 compounds from both National Cancer Institute (NCI) and ZINC databases were discovered as potent inhibitors

Morphometrical study of the cat cerebellum using unbiased design-based stereology

The objective of the present study was to investigate the morphometrical features of the cat cerebellum using design-based stereology. Cerebellar hemispheres from four male cats were examined. Isotropic, uniform random sections were obtained and processed for light microscopy. Cerebellar total volume (V), white (WM) and grey matter (GM) volume fractions, and the volumes of the molecular and granular layers were measured using the Cavalieri's estimator and the point counting system. Cerebellar surface area was estimated using test lines, and Purkinje cellular and nuclear volumes were analysed using the nucleator technique. The volume of the cat cerebellar hemispheres was 2.06 \ub1 0.29 cm3. The relative volume fractions of the GM and WM were 70.6 \ub1 2.6% and 29.3 \ub1 2.6%, respectively. The surface area of the cerebellar hemisphere was 68.2 \ub1 17.8 cm2. The volumes of the molecular and granular layers were estimated at 0.89 \ub1 0.16 cm3 and 0.56 \ub1 0.1 cm3, respectively. The Purkinje cell volumes were found to be ranging from 1,717 to 28,489 \ub5m3, of which cells with a perikaryon volume of 6,994 \ub5m3 had a higher incidence. The Purkinje nuclear volume was estimated at 440\u20133,561 \ub5m3, and nuclei with a volume of 1,252 \ub5m3 were the most frequently occurring ones. Our data might contribute to the veterinary comparative neuroanatomy knowledge, help develop experimental studies in this field, and possibly lead to advancement in the diagnosis and treatment of nervous diseases in the cat