Synthesis and antidiabetic activity of novel triazole derivatives containing amino acids

• Published in: Journal of heterocyclic chemistry 2020-06, Vol.57 (6), p.2365-2378
• Main Authors: Mohamed, Mounir A. A., Abd Allah, Omyma A., Bekhit, Adnan A., Kadry, Asmaa M., El‐Saghier, Ahmed M. M.
• Format: Article
• Language: English
• Subjects: Acetophenone; Aldehydes; Amino acids; Aromatic compounds; Benzaldehyde; Body weight; Derivatives; Diabetes mellitus; Glucose; In vivo methods and tests; Insulin; Sulfonamides; Triazoles
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.3951

New series of triazole derivatives coupled with amino acids 1a‐h were obtained via multicomponent reaction of 2‐hydroxy benzaldehyde or 2‐hydroxy acetophenone with thiosemicarbazide and different amino acids. The obtained compounds were reacted with p‐toluinesulfonyl chloride 2 to give the corresponding sulfonamides 3a‐h. Compound 1b was allowed to react with different aromatic aldehydes or cyclic ketone under alkaline conditions to afford the expected imino compounds 4a‐d and 6a‐c, respectively. These compounds were allowed to react with ethyl glycolate to yield the expected thiazolidinone derivatives 5a‐d or 7a‐c, respectively. Structures of the newly synthesized compounds were found to be in accordance with their elemental analyses and spectral data. The obtained compounds exhibited very prominent in vitro and in vivo antihyperglycemic effect at a dose of 40 mg/kg body weight compared to the standard drug gliclazide and control. The antidiabetic effect was investigated using oral glucose tolerance test in normal and non‐insulin‐dependent diabetes mellitus (NIDDM) in STZ‐rat model. Compounds 3a‐h, 5b, 5c, 5d, 7a, 7b, and 7c showed significant activity in lowering blood glucose (more than 80%) compared to the NIDDM control.