Synthesis, biological evaluation, and computational analysis of fused bis-thiadiazole analogues as potential anti-Alzheimer’s and antidiabetic agents

Fused bis -thiadiazole analogues (1–20) was synthesized, characterized through ¹HNMR, ¹³CNMR and HR-EIMS and evaluated against acetylcholinesterase, butyrylcholinesterase, α-glucosidase and α-amylase enzymes. All compounds demonstrated inhibitory activity against AChE and BuChE, with IC₅₀ values ranging from 4.20 to 27.05 µM and 6.40 to 32.08 µM, respectively as compared to reference drug Allanzanthane (IC₅₀ = 14.11 and 16.02 µM, respectively). In a similar manner, significant inhibition was observed against α-glucosidase and α-amylase, with IC₅₀ values ranging from 3.30 to 29.20 µM and 7.07 to 32.40 µM, respectively as compared to standard drug acarbose (IC₅₀ = 14.11 and 18.05 µM). Analogues 8 and 12 emerged as most effective inhibitors of AChE and BuChE, while analogues 1 and 5 exhibited the highest activity against α-glucosidase and α-amylase enzymes. Molecular docking was conducted, revealing strong binding affinities and favourable interactions of most active derivatives within active sites of their respective target enzymes.