d‑Glucose-Conjugated Benzo[d]thiazole-thiazolidin-4-one Hybrids: Design and Synthesis as Multitarget Anti-Alzheimer Compounds.

A new series of d-glucose-conjugated 2,3-thiazoline-benzo-[d]-thiazole hybrid compounds 8a-k were synthesized from reaction of the corresponding thioureas 7a-k and ethyl bromoacetate in the presence of sodium acetate in chloroform. The evaluations for anti-Alzheimer activity showed that some compounds exhibited remarkable inhibitory activity against AChE and BChE as well as against MAO-A and MAO-B enzymes. The orders of inhibition for each enzyme of these compounds were as follows: 8j > 8h (against AChE), 8k > 8b (against BChE), 8k > 8g > 8f (against MAO-A), and 8e > 8c (against MAO-B). Compound 8k was an inhibitor of interest due to its potent or good activity against the two studied enzymes BChE and MAO-B, respectively. Compounds 8j (against AChE) and 8k (against (BChE) had a competitive type with K i constants of 16.93 and 17.09 nM, respectively. The most potential compounds 8c, 8j, and 8k were not cytotoxic on 3T3 cells and had high levels of safety.