Anxiolytic effect of 2-oxyindolin-3-glyoxylic acid derivatives: computer prediction and experimental confirmation

Aim. To complete the computer prediction of possible spectrum of biological activity of simple amides of 2-oxyindolin-3-glyoxylic acid derivatives and to test their anxiolytic activity in experiment. Methods. The prediction of possible spectrum of biological activity of simple amides of 2-oxyindolin-3-glyoxylic acid derivatives was performed using PASS (Prediction of Activity Spectra for Substances) software. The experimental part was performed on 140 adult rats of both sexes. Animals were distributed to subgroups (n=10 in each subgroup) according to age and gender. Experimental screening for anxiolytic action was performed using the Vogel’s «conflict situation» method. Results. 12 compounds highly potential for anxiolytic activity were selected after the computer prediction. Glutamate, serotonin, aspartate receptors blockade, gamma-aminobutyric acid (GABA)-receptors stimulation and depression of GABA-aminotransferase were in the list of possible mechanisms of action. Along with anxiolytic activity anticonvulsive, antipsychotic, antihypoxic and hypnotic effects were predicted. During the Vogel’s «conflict situation» test, 2-Hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide, 2-Hydro-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-N-phenyl-acetamide and N-[(2-Oxo-1,2-dihydro-indol-3-ylidene)-phenethylcarbamoyl-methyl]-benzamide had significantly decreased the latent time for taking water from drinking place. At the same time, 2-Hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide, 2-Hydro-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-N-phenyl-acetamide, N-[(2-Oxo-1,2-dihydro-indol-3-ylidene)-phenethylcarbamoyl-methyl]-benzamide and 3-Hydroxy-3-(2-oxo-cyclohexylmethyl)-1-piperidin-1-ylmethyl-1,3-dihydro-indol-2-one compounds had significantly increased the number of punished attempts for getting water, assuming anxiolytic activity. Among 2-oxyindolin simple amides derivatives 2-Hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide had the strongest anxiolytic effect in test with punished behavior. Conclusion. Computer prediction of 2-oxyindolin-3-glyoxylic acid derivatives anxiolytic effect was confirmed experimentally.

planned medication studies, 2-oxyindol-3-glyoxylic acid derivatives, computer prediction, anxyolitic effect, «conflict situation» test