Synthesis, in vitro and in silico evaluation of indole linked carbohydrazides and 1,3,4-oxadiazoles as new α-glycosidase inhibitors
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Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
The Hemetsberger indole reaction afforded 6-methyl and methoxy substituted indole-2-carboxylates 8 which were then reacted with an excess of hydrazine hydrate in ethanol to produce indole-2-carbohydrazides 9. Treatment of the compounds 9 with a range of commercially available benzoyl chlorides generated new indole linked diacyl hydrazines 10-15 and the corresponding cyclodehydration reaction in the presence of N,N-diisopropylethylamine (DIPEA) and p-toluenesulfonyl chloride (p-TsCl) in acetonitrile gave the targeted indole linked 1,3,4-oxadiazoles 16-21. The antidiabetic properties of the newly synthesized compounds were evaluated by employing alpha-glycosidase and alpha-amylase enzyme inhibition assays and the targeted compounds showed a range of inhibitory activities against alpha-glycosidase and alpha-amylase. The study revealed that the compounds selectively inhibit alpha-glycosidase enzyme. The detection of selective inhibition behaviours for alpha-glycosidase enzyme increased the novelty of the study and most of the IC50 values against the designated enzyme were found to be better than the standard acarbose. The structure-activity relation study illustrated that the oxadiazole ring with the methyl substituted indole and nitro substituted benzene rings demonstrated the best inhibition towards the alpha-glycosidase enzyme. The detected IC50 value for the identified compound 21 was found to be better (>25-fold) than the standard acarbose.
Açıklama
Anahtar Kelimeler
Indole, 4-oxadizole, Carbohydrazide, alpha-glycosidase, alpha-amylase, Selective inhibition
Kaynak
Journal of Molecular Structure
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
1325
