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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 &lt; 0.0001). However, compound 5a increased urinary 8-OHdG levels. The lethal dose (LD 50 ) 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 LD 50 was &gt;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.

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