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ANTHELMINTIC ACTIVITY OF NOVEL ARYLSALICYLAMIDE DERIVATIVES

DOI: https://doi.org/10.29296/25419218-2019-04-09
Issue: 
4
Year: 
2019

D.P. Sevbo , A.Yu. Malakhova, V.N. Kuklin Saint Petersburg State Chemopharmaceutical University, 14, Prof. Popov St., Lit A, Saint Petersburg 197376, Russian Federation

Introduction. The incidence of intestinal helminthiases ranks fourth among diseases and injuries. Analysis of a range of anthelmintic drugs has shown that most of the agents registered in the Russian Federation are manufactured in foreign countries; the main drugs of which are salicylamide derivatives. Objective: to synthesize novel substituted salicylic acid amides with anthelmintic activity and to establish a structure-biological activity relationship. Material and methods. To identify the synthesized compounds, their melting point, UV and IR spectra in potassium bromide disks, and 1H NMR spectra in a DMSO-d6 solution were determined. Various methods for chromatographic analysis, such as TLC, GLC, HPLC, were also employed. Biological activity and toxicity were investigated in male albino mice. Results. The synthesized arylsalicylamides were found to have a higher anthelmintic activity than fenasal. Their acute toxicity (LD50) was determined; most of the synthesized compounds were practically non-toxic. A study of the relationship of their anthelmintic activity and toxicity to the structure showed that the amides containing chlorine atoms in the acid fragment were more active than those containing bromine atoms; replacing the methyl group in an amide to the alkoxy group in the arylamine fragment led to a decrease in acute toxicity and an increase in anthelmintic activity. Acetylation of phenolic hydroxyl arylsalicylamides reduced acute toxicity. Conclusion. The relationship of the anthelmintic activity and toxicity of arylsalicylamides to their structure was studied, which showed how the nature of the substituent in the salicyloyl and arylamine fragments affected toxicity and anthelmintic activity. 2,4-dichloro-6-([4-methyl-3-chlorophenyl] carbamoyl)phenyl acetate was proposed to extend tests.

Keywords: 
arylsalicylamide derivatives
toxicity
relationship
structure
activity

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