Synthesis and evaluation of analgesic/anti-inflammatory and antimicrobial activities of 3-substituted-1,2,4-triazole-5-thiones


TOZKOPARAN B., KUPELI E., YEŞİLADA E., Isik S., ÖZALP M., Ertan M.

ARZNEIMITTELFORSCHUNG-DRUG RESEARCH, vol.55, no.9, pp.533-540, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 9
  • Publication Date: 2005
  • Journal Name: ARZNEIMITTELFORSCHUNG-DRUG RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.533-540
  • Hacettepe University Affiliated: Yes

Abstract

In this study, the synthesis of a novel series of Mannich bases of 5-mercapto-3-aryl-1,2,4-triazoles is described. The structures attributed to compounds la 5e were elucidated using IR and H-1-NMR spectroscopic techniques besides elemental analysis. The formation of 1-aminomethyl-3 -substituted- 1,2,4-triazole-5-thiones - not the isomeric 3-substituted-4-aminomethyl-1,2,4-triazole-5-thiones was unambiguously confirmed by X-ray crystallographic analysis of 1c. The compounds were examined for their in vivo anti-inflammatory and analgesic activity in two different bioassays, namely carrageenan-induced hind paw edema and phenzoquinone-induced abdominal constriction tests in mice, respectively. In addition, the ulcerogenic effects of the compounds were determined. Among the tested derivatives most promising results were obtained for the compounds bearing a nonsubstituted phenyl group at C-3 position of the triazole ring (1a-e). The compounds were also evaluated for their in vitro antimicrobial activity against a series of gram positive bacteria [Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212) 1, gram negative bacteria [Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853)] and yeast-like microorganisms [Candida albicans (ATCC 90028), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019)]. One series of the examined compounds (3a-e) exhibited better antibacterial activity especially against gram positive bacteria than against gram negative bacteria. Compounds 2c, 3b, and 3e were found to be more effective against C parapsilosis compared with the other derivatives (MIC: 16 pg/ mL).