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.
Highlights
Many substituted 1,2,3-thiadiazoles and derivatives were prepared, but few of them showed high antibacterial activity [1]
New 1,2,3-thiadiazole, and 1,2,3-selenadiazole derivatives were prepared using the methods that were previously established by Hurd and Mori for 1,2,3-thiadiazole preparation and by Lalezari et al
The semicarbazone derivatives (4a, 4b) which were prepared from the condensation reaction of the corresponding ketones (3a, 3b) and semicarbazide hydrochloride were used in the preparation of the 1,2,3-thiadiazole (5a, 5b) and 1,2,3-selenadiazole derivatives (6a, 6b)
Summary
Many substituted 1,2,3-thiadiazoles and derivatives were prepared, but few of them showed high antibacterial activity [1]. The concept of isosteric exchange was long used as a tool for modifying the activity of biologically important molecules. One such important isosteric pair is sulfur and selenium, which were incorporated as heteroatoms in the heterocyclic system [2]. 1,2,3-selenadiazole compounds were reported to possess antibacterial, antifungal [1,3,4], antiviral [5], and anticancer [6] activities. The current study assessed the activity of newly prepared 1,2,3-thiadiazole. The genotoxicity of the newly synthesized compounds was measured using the
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