<scp>d</scp>-Glucose-Conjugated Benzo[<i>d</i>]thiazole–thiazolidin-4-one Hybrids: Design and Synthesis as Multitarget Anti-Alzheimer Compounds

A new series of d-glucose-conjugated 2,3-thiazoline-benzo-[<i>d</i>]-thiazole hybrid compounds <b>8a</b>-<b>k</b> were synthesized from reaction of the corresponding thioureas <b>7a</b>-<b>k</b> 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: <b>8j</b> > <b>8h</b> (against AChE), <b>8k</b> > <b>8b</b> (against BChE), <b>8k</b> > <b>8g</b> > <b>8f</b> (against MAO-A), and <b>8e</b> > <b>8c</b> (against MAO-B). Compound <b>8k</b> was an inhibitor of interest due to its potent or good activity against the two studied enzymes BChE and MAO-B, respectively. Compounds <b>8j</b> (against AChE) and <b>8k</b> (against (BChE) had a competitive type with <i>K</i> _i constants of 16.93 and 17.09 nM, respectively. The most potential compounds <b>8c</b>, <b>8j</b>, and <b>8k</b> were not cytotoxic on 3T3 cells and had high levels of safety.