New thiophene-1,2,4-triazole-5(3)-ones: Highly bioactive thiosemicarbazides, structures of Schiff bases and triazole–thiols

• Published in: European journal of medicinal chemistry Vol. 84; pp. 639 - 650
• Main Authors: Ünver, Yasemin, Sancak, Kemal, Çelik, Fatih, Birinci, Emrah, Küçük, Murat, Soylu, Serkan, Burnaz, Nesibe Arslan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 12-09-2014
• Subjects: 1,2,4-Triazole/thiol; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial; Antioxidant; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Bacillus cereus - drug effects; Dose-Response Relationship, Drug; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium smegmatis - drug effects; Schiff base; Schiff Bases - chemistry; Semicarbazides - chemistry; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Sulfhydryl Compounds - chemistry; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacology; Thiosemicarbazide; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Schiff base; Antimicrobial; Thiosemicarbazide; 1,2,4-Triazole/thiol; Antioxidant
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.01.014

Key compound 2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole-1-yl) acetohydrazide (3) was synthesized by reacting hydrazine hydrate with ethyl-2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole-1yl)acetate (2), obtained in basic media from 4-amino-5-(thiophene-2-ylmethyl)-2H-1,2,4-triazole-3(4H)-one (1). Compound 3 was converted to thiosemicarbazide derivatives (4a–d) and Schiff base derivatives 6a–e and 7a–e. The treatment of compound 4 with NaOH gave 4-amino-2-((4-(4-aryl)-5-mercapto-4H-1,2,4-triazole-3-yl)methyl)-5-(thiophene-2-ylmethyl)-2H-1,2,4-triazole-3(4H)-ones (5a–d). All newly compounds, well characterized by elemental analyses, IR, 1H NMR, 13C NMR and mass spectral studies were tested for their antioxidant and antimicrobial activities. Thiosemicarbazide derivatives (4a–d) were highly active in two antioxidant tests with 69.0–88.2% DPPH scavenging and 503–1257 μM TEAC values, while the others showed lower or no activity. The results of the two antioxidant tests correlated well. Moreover, Thiosemicarbazide derivatives (4a–d) also showed antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Mycobacterium smegmatis. Thiosemicarbazide group deserves attention in the synthesis of bioactive compounds.
[Display omitted] Twenty novel triazole derivatives were synthesized. Compounds 4a–d possessing triazole and thiosemicarbazide exhibited both antioxidant and antimicrobial activities. Crystal structures of 2 and 4d were determined.
•Bioactive 1,2,4-triazole-5(3)-one derivatives were synthesized.•The compound 2 and 4d were characterized by elemental analyses, IR, 1H NMR, 13C NMR and X-ray crystallography.•All the compounds were tested for antimicrobial and antioxidant activities.•Thiosemicarbazide group deserves attention in the synthesis of bioactive compounds.