Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study

Rafaqat Hussain, Mazloom Shah, Shahid Iqbal, Wajid Rehman, Shoaib Khan, Liaqat Rasheed, Haseena Naz, Hanan A. Al-ghulikah, Eslam B. Elkaeed, Rami Adel Pashameah, Eman Alzahrani, Abd Elaziem Farouk

Research output: Journal PublicationArticlepeer-review

9 Citations (Scopus)

Abstract

Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1–25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 μM (against α-amylase) in comparison to standard acarbose (12.80 ± 0.10 μM). Similarly, synthetics analogs also displayed a varied range of α-glucosidase activity ranging from 0.80 ± 0.01 μM to IC50 = 29.70 ± 0.40 μM (against α-glucosidase) as compared to standard acarbose (IC50 = 12.90 ± 0.10 μM). Among synthesized analogs, compound 22 showed excellent potency due to the presence of di-hydroxy substitutions at the 2,3-position of the aryl ring. For all analogs, the structure–activity relationship was carried out based on the pattern of substitutions around the aryl ring, and further, the potent analogs were subjected to a molecular docking study to analyze how active residues of targeted enzymes interact with active parts of newly prepared analogs. The result obtained shows that these compounds furnish several key interactions with enzyme active sites and, hence, enhanced their enzymatic activities.

Original languageEnglish
Article number1023316
JournalFrontiers in Chemistry
Volume10
DOIs
Publication statusPublished - 6 Oct 2022
Externally publishedYes

Keywords

  • 4-benzodioxin
  • molecular docking
  • synthesis
  • thiadiazole-fused-[1,4]-thiadiazole
  • α-amylase
  • α-glucosidase

ASJC Scopus subject areas

  • Chemistry (all)

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