Synthesis, α-glucosidase inhibitory activity, and molecular docking of cinnamamides

Nur Pasca Aijijiyah, First Ambar Wati, Reni Rahayu, Alfatchu Srilistiani, Farah Mahzumi, Tinezsia Aulia, Liangga Santoso, Egar Pamela, Ersya Yanu Ramadhani, Yan Alamanda Ilfahmi, Adi Setyo Purnomo, Surya Rosa Putra, Eko Santoso, Sri Ningsih, Nisrina Firdausi, Mardi Santoso*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Suitably substituted cinnamamides (3a-n) were successfully synthesized and tested for α-glucosidase inhibitory activity. Nine of the synthesized cinnamamides (3a-f, k-m) displayed moderate inhibitory activity, which was better than acarbose (IC50 = 185.00 ± 9.4 µM), with IC50 values ranging from 44.43 ± 5.7 to 91.14 ± 11.4 µM. Their α-glucosidase inhibitory activity greatly depended on their structure with electron-withdrawing groups on the cinnamoyl aromatic ring causing increased inhibition activity. According to the in vitro assay results, compound 3b with p-dimethylamino on the cinnamoyl ring has the best α-glucosidase inhibitory activity. The new synthesized cinnamamides (3b-i) showed acceptable physicochemical and pharmacokinetics characteristics with little toxicity indicating their potential use as lead drug candidates. Molecular docking studies of compound 3b (binding energy −8.33 kcal/mol) revealed that it interacted with His626 and two catalytic residues of α-glucosidase, namely Asp469 and Asp568. Overall, these cinnamamides show potential as lead structures for further optimization as α-glucosidase inhibitors. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)723-735
Number of pages13
JournalMedicinal Chemistry Research
Volume32
Issue number4
DOIs
Publication statusPublished - Apr 2023

Keywords

  • Acarbose
  • Cinnamamides
  • Molecular docking
  • α-Glucosidase inhibitory activity

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