Water extract rice husk as an efficient catalyst to synthesis of p-thymol tailored 1,2,4-triazole sulfanyls as potential antidiabetic candidates
摘要
This study presents a new series of sulfanyl derivatives of 1,2,4-triazole (7a–L), synthesized from 5-((4-isopropyl-3-methylphenoxy)methyl)-4-phenyl-4 H-1,2,4-triazole-3-thiol (5) and substituted alkyl halides (6a–L). A green synthetic approach was developed using rice husk water extract as a catalyst, highlighting the principles of sustainable chemistry. In addition, p-thymol, a naturally occurring phenolic monoterpenoid, was employed in the synthesis of the target compounds to reduce environmental impact and minimize adverse effects. The antidiabetic properties of the target compounds (7a-L) were evaluated. In vitro assays assessing antidiabetic activity against α-amylase and α-glucosidase enzymes revealed that the majority of the compounds demonstrated good to moderate efficacy. Notably, compounds 7b, 7f, and 7 g exhibited the most promising results, with screening indicating that 7b (IC50 = 17.22 ± 0.041 µM), 7f (IC50 = 15.23 ± 0.019 µM), and 7 g (IC50 = 16.27 ± 0.042 µM) showed significant α-glucosidase inhibitory potential, comparable to the standard acarbose (IC50 = 15.48 ± 0.012 µM). Furthermore, the inhibitory effects of 7b (IC50 = 19.24 ± 0.053 µM), 7f (IC50 = 18.72 ± 0.112 µM), and 7 g (IC50 = 19.21 ± 0.081 µM) on α-amylase were also similar to acarbose (IC50 = 14.28 ± 0.014 µM). In silico molecular docking studies suggested that compounds 7a-L exhibited a notable affinity for the active sites of human lysosomal acid glucosidase (HLAG) and pancreatic amylase (HPA), indicating that most of the tested compounds possess potent anti-hyperglycemic activity.
Graphical Abstract