Synthesis and biological evaluation of benzothiazol-based 1,3,4-oxadiazole derivatives as amyloid β-targeted compounds against Alzheimer’s disease

Abstract

A series of new benzothiazol-based 1,3,4-oxadiazole derivatives were synthesized and evaluated for their neuroprotective effects against Aβ25–35-induced toxicity in SH-SY5Y cells. The bioassay results indicated that most of the tested compounds exhibited promising neuroprotective activity. In particular, compound 2-[[[5-[(4-bromophenylmethyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole showed the most potent activity (95.7% of cell viability at 10 μM), better than the positive control EGCG (90.7% of cell viability at 10 μM). Furthermore, compounds 2-[[[5-[(2-bromophenylmethyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole, 2-[[[5-[(4-bromo-2-fluorophenylmethylyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole, and 2-[[[5-[(4-methoxyphenylmethyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole displayed neuroprotective activity similar to EGCG (87.7, 89.1, and 87.7% of cell viability, respectively, at 10 μM). The preliminary SARs analysis indicated that benzene ring is the key factor for the neuroprotective activity and the bromo atom substituted at 4-position of the benzene ring favors the neuroprotective activity. In addition, the fluoro group in the benzene ring appears not beneficial for the neuroprotective activity.