Antidiabetic and Cytotoxicity Studies of Novel Quinazolinone–1,3,4‐Thiadiazole Molecular Hybrids

In the treatment of diabetes mellitus (DM), inhibition of carbohydrate‐hydrolysing enzymes, such as α‐amylase, has emerged as a promising therapeutic strategy. In the present study, a series of quinazolinone‐1,3,4‐thiadiazole molecular hybrids were designed, synthesized and biologically evaluated for their antidiabetic potential. The full structural elucidation of each molecular hybrid was carried out using 1D/2D NMR spectroscopy, FT‐IR and high‐resolution mass spectrometry (HRMS). All the synthesized compounds, including intermediates ( 2a‐c , 3a‐g ) and final hybrids ( 5a‐u ), were tested for α‐amylase inhibition. Compounds 3b and 5t exhibited approximately twofold higher potency than the standard drug acarbose. Cytotoxicity evaluation against hepatocellular carcinoma (HepG2) cells revealed no significant cytotoxicity, with IC 50 values exceeding 100 µM. Furthermore, molecular docking and simulation studies were conducted to analyse the ligand‐receptor interactions, while ADME/T predictions suggested that the most potent compounds possess favourable drug‐like properties and could serve as promising lead candidates for further development.