Discovery of C-12 dithiocarbamate andrographolide analogue as a novel antioxidant and α-glucosidase inhibitors: In vitro and in silico studies
Utid Suriya, Chanathip Duangtha, Thanchanok Dontricharoen, Paveena Yamanont, Sakonwan Kuhaudomlarp, Prawit Thitiyanuwat, Bodee Nutho, Patcharee Arsakhant, Rungnapha Saeeng, Noppawan Phumala Morales, Supachoke Mangmool, Sutharinee Likitnukul
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.
Introduction
Type 2 diabetes mellitus (T2DM) is a non-communicable disease (NCD) caused by insulin resistance, which leads to increased blood glucose levels. Pathophysiology of T2DM is associated with oxidative stress, chronic low-grade inflammation, and the effects of insulin resistance on normal glycemic control. Insulin resistance refers to an impairment of the response to the physiological function of insulin, which is crucial for stimulating glucose uptake in insulin target tissues, including skeletal muscle and adipose tissue.
Materials and methods
Isolation of andrographolide and synthesis of C-12 dithiocarbamate andrographolide analogues
Andrographolide was isolated from Andrographis paniculata with ethyl acetate at room temperature and then confirmed by both 1H NMR and thin-layer chromatography (TLC) compared with a standard andrographolide (Merck, Germany) (Figs 1–2). The extract was washed with hexane and dichloromethane and further recrystallized using methanol.
Results and discussion
In vitro antioxidant screenings
Cellular damage occurs when the equilibrium between free radicals like reactive oxygen species (ROS) and antioxidants is imbalanced. Excessive ROS can damage proteins and lipids within cells, impairing insulin signaling and glucose metabolism, which are critical in the development of diabetes-related complications.
Acknowledgments
We are grateful to the Faculty of Science, Mahidol University, for providing the facilities and institutional support necessary to conduct this research.
Citation: Suriya U, Duangtha C, Dontricharoen T, Yamanont P, Kuhaudomlarp S, Thitiyanuwat P, et al. (2025) Discovery of C-12 dithiocarbamate andrographolide analogue as a novel antioxidant and α-glucosidase inhibitors: In vitro and in silico studies. PLoS One 20(10): e0334026. https://doi.org/10.1371/journal.pone.0334026
Editor: Asif Ali, University of Chicago, UNITED STATES OF AMERICA
Received: April 30, 2025; Accepted: September 21, 2025; Published: October 22, 2025
Copyright: © 2025 Suriya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: National Research Council of Thailand (NRCT): contract no. #N42A660969 (to S.L.), the Agricultural Research Development Agency (ARDA) grant #PRP6605030320 (to R.S.). The Central Instrument Facility (CIF) and Center of Nanoimaging (CNI), Faculty of Science, Mahidol University, #PM-SLI-3-65-05 (to S.L.).
Competing interests: The authors have declared that no competing interests exist.
