ABSTRACT
Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis which involves caspases, a group of cysteine proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 plays a key role in apoptosis and are a therapeutic target for their inhibition. In pursuit of better caspase-3 inhibitors, a quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated by internal and external validation method. The values of statistical data are r = 0.955, F = 72.95, SEE = 0.397, q(2) = 0.885, S(PRESS) = 0.44. The present study reveals that when the conformational minimum energy is increased, and lowest unoccupied molecular orbital energy and highest occupied molecular orbital energy are decreased the biological activity can be increased. On the basis of a selected QSAR model, we designed a new series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines compounds, calculated their caspases inhibitory activity and found that the designed compounds were more potent than the existing compounds.
Subject(s)
Caspase Inhibitors , Quantitative Structure-Activity Relationship , Quinolines/pharmacology , Drug Design , Humans , Quinolines/chemistryABSTRACT
A new, simple, sensitive, precise and robust high-performance thin layer chromatographic (HPTLC) method was developed for the estimation of conessine in herbal extracts and pharmaceutical dosage forms. Analysis of conessine was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with mobile phase consisting of toluene-ethylacetate-diethyl amine (6.5:2.5:1, v/v/v) at room temperature (25+/-2 degrees C). After derivatized the plate with modified Dragendroff's reagent, Camag TLC scanner III was used for spectrodensitometric scanning and analysis of the plate in absorbance mode at 520 nm. The system was found to give compact spots for conessine (Rf value of 0.82). The data for calibration plots showed good linear relationship with r2=0.9998 in the concentration range of 1-10 microg with respect to peak area. The present method was validated for precision and recovery. The limits of detection and quantification were determined. Statistical analysis of the data showed that the method is reproducible and selective for estimation of conessine.
