Synthesis and biological activity of 1,3,4-oxa(thia)diazole, 1,2,4-triazole-5-(thio)one and S-substituted derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid

• Published in: Research on chemical intermediates 2016-05, Vol.42 (5), p.4459-4477
• Main Authors: Tumosienė, I., Jonuškienė, I., Kantminienė, K., Šiugždaitė, J., Mickevičius, V., Beresnevičius, Z. J.
• Format: Article
• Language: English
• Subjects: Catalysis; Chemistry; Chemistry and Materials Science; Inorganic Chemistry; Physical Chemistry
• ISSN: 0922-6168; 1568-5675
• DOI: 10.1007/s11164-015-2290-0

A series of novel derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid bearing two identical substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole, or 1,2,4-triazole moieties were synthesized and their molecular structures were confirmed by IR, 1 H, 13 C NMR spectroscopy, and elemental analysis data. The synthesized compounds were screened for their reducing power, free radical scavenging, plant growth regulating, and antimicrobial properties. 5,5′-((Phenylazanediyl)bis(ethane-2,1-diyl))bis(4-phenyl-2,4-dihydro-3 H -1,2,4-triazole-3-thione) showed excellent antioxidant activity, three times higher than that of the antibiotic control (cefazolin). 2,2′-(((Phenylazanediyl)bis(ethane-2,1-diyl))bis(4-phenyl-4 H -1,2,4-triazole-5,3-diyl))bis(sulfanediyl))diacetate exhibited notable bactericidal activity against Pseudomonas aeruginosa with MBC and MIC values 7.3 µg/ml, whereas 12 compounds displayed significant fungicidal activity against Candida albicans with MIC value 3.9 µg/ml. Graphical Abstract Synthesis of compounds 2 – 27 . R: 2 , 5 , 7, 10, 13, 15-27 C 6 H 5 –; 3 , 8 , 11 4-Cl-C 6 H 4 –; 4 , 9 , 12 CH 3 –; 6 , 14 2.6-(CH 3 ) 2 -C 6 H 3 –; R′: 15 CH 3 CH 2 –; 16 (CH 3 ) 2 CH–; 17 (CH 3 ) 2 CHCH 2 –; 18 CH 3 CH 2 CH 2 CH 2 –; 19 (CH 3 ) 2 CHCH 2 CH 2 –; 20 CH 3 CH 2 CH 2 CH 2 CH 2 –; 21 NH 2 COCH 2 –; 22 C 6 H 5 CH 2 –; 23 C 6 H 5 COCH 2 –; 24 4-ClC 6 H 4 COCH 2 –; 25 4-NO 2 C 6 H 4 COCH 2 –; 26 C 2 H 5 OCOCH 2 –.