2-(Aralkylated/Arylated/Arenylatedthio) 5-Benzyl-1, 3, 4-Oxadiazoles: As Less Cytotoxic And Moderate Inhibitors Of Cholinesterases

1, 3, 4-Oxadiazoles are known to possess diverse biological activities and proposed synthetic methodology was aimed to synthesize biologically active 1, 3, 4-oxadiazole-2-thiols derivatives. It was instigated by converting 2-phenylacetic acid (1) to ethyl-2-phenylacetate (2) by Fischer esterification method. The ester underwent hydrazinolysis to afford 2-phenylacetohydrazide (3) which was transformed via ring closure with carbon disulfide in alcoholic base to achieve 5-benzyl-1,3,4-oxadiazole-2-thiol (4). Finally, the parent oxadiazole 4 was reacted with a variety of aralkylated/arylated/arenylated halides (5a-i) in polar aprotic solvent; N,Nˈ-dimethylformamide (DMF) and lithium hydride (LiH) which acted as base under to afford 2- (aralkylated/arylated/arenylatedthio) 5-benzyl-1,3,4-oxadiazoles (6a-i). The synthesized derivatives were screened against acetyl/butyrylcholinesterases for enzyme inhibitory potential. The incorporation of 3-nitro/4-nitrophenyl moieties on S-position of parent oxadiaozle demonstrated decent inhibitory potential against cholinesterases while rest displayed weak inhibition relative to reference standard Eserine. The LD₅₀ data revealed that most of the derivatives were found to be less cytotoxic relative to standard doxorubicin