ON THE QUESTION OF THE SAFETY OF A 4-ALKYL-SUBSTITUTED COMPOUND WITH ANTI-TUMOUR ACTION

Abstract

The aim was to investigate the acute toxicity of the AX-554 compound following its intragastric administration, as well as to determine the effective cytotoxic concentration and dose of this preparation.Materials and methods. The study was performed using 76 nonlinear white laboratory mice of both sexes weighing 18–22 g, 150 male mice of C57BL/6 line and LCC tumour cell culture. The acute toxicity of the AX-554 4-alkyl-substituted compound in the form of granulated pellet mass was studied following its intragastric administration, with the results being analysed according to Litchfield and Wilcoxon. The effective dose of the substance was determined using a syngeneic tumour model in C57Bl/6 male mice with inoculated Lewis lung carcinoma. The effective concentration of the compound was determined in a tumour cell culture.Results. Our study of the acute toxicity of AH-554 after its intragastric administration in the form of granulate tablet mass have confirmed AH-554 to be a non-toxic substance. In doses ranging from 21.2 to 384 mg/kg, AH-554 is observed to suppress tumour growth in mice with syngeneic lung carcinoma at a level from 20 to 90%, with the highest therapeutic dose exceeding the minimum effective one by more than 18 times. This pattern is also observed when AH554 is applied in the culture of tumour cells. The results of this study can be used for developing a pharmaceutical based on the AH-554 compound.Conclusion. The AH-554 compound, 2-amino-4H-chromene derivative, is characterized by an optimal safety profile due its low toxicity and a wide range of anti-tumour action.

Keywords

• 2-amino-4h-chromene compound
• acute toxicity
• intragastric administration
• widerange anti-tumour activity
• lewis lung carcinoma