Biological activity of dithioacids and thioamides of the benzimidazole series

Abstract

The aim of this work is the synthesis of benzimidazole derivatives (dithioacids and thioamides) and the subsequent screening of the biological activity of the synthesized compounds for antibacterial, antiprotozoal and antimycotic activities. We obtained benzimidazole dithioacids by the action of sulfur and potassium carbonate on 2-mercaptomethyl-benzimidazoles using dimethylformamide as a reaction medium. To obtain thioamides, an appropriate primary or secondary amine was additionally introduced into the reaction medium. Regarding the effect of the substituents on the biological activity, the following should be noted: dithioacids (compounds 1-4) exhibited a more pronounced activity as compared to thioamides (5-13) both in terms of the number of susceptible microorganisms and the amount of activity; in particular, only compounds 1 and 2 exhibited activity toward all the objects studied, while thioamides 5-13 showed no detectable fungistatic activity and only in one case (compound 10) some activity toward gram-negative microorganisms. The calculations showed the following: dithioacids' antibacterial activity toward St. aureus was 37%, 44% for compound 1, 44% for compound 2, and 29% for compound 3; toward E. coli the dithioacids' antibacterial activity toward compound 1 was 32%, 40% for compound 2, 28% for compound 3, and 32% for compound 4. The fungistatic activity of the dithioacids was 30% for compound 1 and 15% for compound 2 compared to that of fundazole. The striking difference in the activity of free dithioic acid 2 (>500 µg/ml) and its salts 3 and 4 (7.8 and 15.6 µg/ml) toward Colpoda is remarkable. Since dithioacid salts are easily oxidized, it can be assumed that it is the oxidation products of the initial salts that have activity as a result of the action of Colpoda oxidase enzymes. The antiprotozoal activity of compound 3 is eight times higher than that of toltrazuril, the activity of compound 4 is four times higher than that of toltrazuril. Benzimidazole thioamides 5, 9, 10, 13 have equal antiprostocidal activity as toltrazuril. The high reactivity of the synthesized compounds will allow their modification in order to enhance their useful properties. The obtained dithioacids and thioamides of benzimidazole series can be used for extended toxicological and pharmacological studies in order to develop methods of animal treatment for diseases complicated by pathogenic and conditionally pathogenic microflora.