Discovery of C-12 dithiocarbamate andrographolide analogue as a novel antioxidant and α-glucosidase inhibitors: In vitro and in silico studies
Issued Date
2025-10-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-105019219226
Journal Title
Plos One
Volume
20
Issue
10 October
Rights Holder(s)
SCOPUS
Bibliographic Citation
Plos One Vol.20 No.10 October (2025)
Suggested Citation
Suriya U., Duangtha C., Dontricharoen T., Yamanont P., Kuhaudomlarp S., Thitiyanuwat P., Nutho B., Arsakhant P., Saeeng R., Morales N.P., Mangmool S., Likitnukul S. Discovery of C-12 dithiocarbamate andrographolide analogue as a novel antioxidant and α-glucosidase inhibitors: In vitro and in silico studies. Plos One Vol.20 No.10 October (2025). doi:10.1371/journal.pone.0334026 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112765
Title
Discovery of C-12 dithiocarbamate andrographolide analogue as a novel antioxidant and α-glucosidase inhibitors: In vitro and in silico studies
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Type 2 diabetes mellitus (T2DM) is a global health issue associated with oxidative stress, inflammation, and insulin resistance‧ Even though α-glucosidase inhibitors such as acarbose are used in treatment, their efficacy is limited by gastrointestinal side effects‧ In this study, we evaluated the antioxidant properties and α-glucosidase inhibition of C-12 dithiocarbamate andrographolide analogues compared to the parent compound, andrographolide‧ Among all analogues, compound 3f exhibited strong antioxidant activity, achieving 84% DPPH inhibition and a reducing antioxidant power activity of 254 μM ascorbic acid equivalent (AAE) at 500 μM‧ Additionally, molecular docking suggested a favorable binding to both yeast and human α-glucosidase at a comparable level as andrographolide, verified by the surface plasmon resonance (SPR) detection system, indicating a strong binding affinity with a dissociation constant (K<inf>D</inf>) of 12‧86 μM‧ It also retains favorable physicochemical properties that align with drug-likeness based on Lipinski’s Rule‧ Functional assay confirmed its inhibitory activity with an IC<inf>50</inf> of 411 μM against the yeast α-glucosidase enzyme model, which was greater than both andrographolide and acarbose‧ Further molecular dynamics (MD) simulation analysis revealed that compound 3f exhibited stable and thermodynamically favorable binding to human α-glucosidase as well as interacting with key amino acids similar to those of andrographolide, providing a preliminary understanding of its potential relevance in a human enzyme context‧ Altogether, these findings highlight the significant potential of compound 3f as a novel α-glucosidase inhibitor, offering a potential therapeutic alternative and paving the way for further anti-diabetic drug development.