Synthesis, Characterization, Antimicrobial Activity, and Genotoxicity Assessment of Two Heterocyclic Compounds Containing 1,2,3-Selena- or 1,2,3-Thiadiazole Rings

Abstract

New 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives, (4-[4-((4-bromobenzyl)oxy)-phenyl]-1,2,3-thiadiazole (5a), 4-[4-((4-chlorobenzyl)oxy)-phenyl]-1,2,3-thiadiazole (5b)), (4-[4-((4-bromobenzyl)oxy)-phenyl]-1,2,3-selenadiazole (6a), and 4-[4-((4-chlorobenzyl)oxy)-phenyl]-1,2,3-selenadiazole (6b)), were prepared and screened in vitro for their antimicrobial activity against various pathogenic microbes. In addition, two compounds (5a and 6a) were examined for their in vivo genotoxicity using rats and an 8-hydroxy-2′-deoxyguanosine (8-OHdG) assay. Compounds 5a and 5b were found to be highly active against Gram-positive and Gram-negative bacteria. In addition, a significant inhibition of urinary 8-OHdG level (50.2%) was observed upon treatment of animals with 500 mg/kg body weight (b.w.) of compound 6a (p < 0.0001). However, compound 5a increased urinary 8-OHdG levels. The lethal dose (LD50) values for compounds 5a and 6a were determined by an up-and-down procedure (OECD 425; OECD 1998), which showed that these compounds are safe, since the LD50 was >5000 mg/kg b.w. Thus, the tested compounds might have the potential for use as antibiotics, since they have low genotoxicity and strong antimicrobial activity.

Keywords

• thiadiazole rings
• heterocyclic compounds
• synthesis
• characterization
• antimicrobial activity
• genotoxicity