Design and Biological Investigation of Novel Pyridine-Sulfonate Hybrids Derived from Natural Monoterpenoids

A series of novel pyridine‑linked sulfonate derivatives (2a–2j) derived from the natural monoterpenoids thymol and carvacrol were designed and synthesized using an efficient one‑pot synthetic strategy. The target compounds incorporated a 3‑chloro‑2‑hydrazinopyridine pharmacophore and were obtained in good yields (83–88%). Structural characterization was performed using FT‑IR, 1H NMR, 13C NMR and mass spectrometry. The synthesized derivatives were evaluated for their in vitro α‑amylase inhibitory, antioxidant and antimicrobial activities. Several compounds demonstrated promising biological potential. In particular, compounds 2a, 2c, 2f and 2h showed significant α‑amylase inhibition, whereas compounds 2b, 2e, 2g and 2j exhibited strong antioxidant activity in the DPPH assay comparable to standard antioxidants. Molecular docking studies were carried out against the isomaltase enzyme (PDB ID: 3A47) to understand ligand–protein interactions, revealing favorable binding affinities for compounds 2a and 2j. In addition, in silico pharmacokinetic and ADME predictions suggested acceptable drug‑likeness and oral bioavailability profiles for most derivatives. These findings suggest that pyridine‑linked sulfonate hybrids of thymol and carvacrol may serve as promising scaffolds for further development of antidiabetic therapeutic agents.