Design, Synthesis, Spectral Characterization and Biological Evaluation of Semisynthetic Andrographis paniculata and its Derivatives

Abstract

Andrographis paniculata (Burm. f.) Nees is an important medicinal plant belonging to the family Acanthaceae and is widely used in traditional systems of medicine. Commonly known as the “King of Bitters,” the plant is characterized by its intensely bitter taste and diverse phytochemical composition. It contains several bioactive constituents, among which andrographolide, a labdane diterpenoid represents a chemically versatile scaffold for the development of bioactive derivatives with potential therapeutic applications. This research describes the synthesis and biological evaluation of four semisynthetic derivatives, designated L-1–L-4, using infrared (IR) spectroscopy, proton nuclear magnetic resonance (¹H-NMR), mass spectrometry, molecular docking, and in-vitro α-glucosidase and α-amylase inhibition assays. These complementary approaches were employed to investigate the derivatives reported structural features and their potential enzyme-inhibitory activities. The research reports mass-to-charge (m/z) values of 407.27, 435.30, 457.28 and 423.30 for L-1, L-2, L-3 and L-4, respectively. Among the tested derivatives, L-2 exhibited the greatest reported inhibitory activity, with IC₅₀ values of 15 µM against α-glucosidase and 22 µM against α-amylase. L-3 showed the next most favourable activity, with corresponding IC₅₀ values of 20 and 28 µM. In contrast, L-1 and L-4 were reported to be less active, although their IC₅₀ values were presented as a broad range of 50–100 µM rather than as compound-specific measurements. Molecular docking results further suggested favourable interactions for L-2 and L-3, including proposed hydrogen-bonding contacts involving hydroxyl and carbonyl groups. Collectively, these preliminary findings identify L-2 and L-3 as promising candidates for further investigation.