SYNTHESIS OF NEW NICOTINIC ACID DERIVATIVES AND STUDYINY THEIR EFFECTS ON CHO HINESTEEAS ENZYWR ACTIVITY

Abstract

The nicotinic acid is refluxed with thionyl chloride to give acid chloride, which is converted to acid hydrazide by treatment with hydrazine hydrate. Thiosemicarbazone and 4-phenyl-thiosemicarbazone are synthesized by treatment of acid chloride with thiosemicarbazide and acid hydrazide with phenyl isothiocyanate, respectively. The cyclization of thiosemecarbazone is achieved by using H2SO4 and NaOH to give 1,3,4-thiadiazole derivative and 1,3,4-triazole derivative respectively. The acid hydrazide is also converted into 5-marcapto 1,3,4-Oxadiazole by refluxing with CS2 and KOH in absolute ethanol, then thiol group is converted into hydroxyl group by treating with H2O2 and formic acid. IR and U.V spectra were used to characterize the prepared compounds. Effect of the synthesized compounds on human serum ChE activity was studied, the results show that all compounds (except compound A2) cause inhibition to the enzyme activity. Kinetic parameters were studied and the results show that compounds (A1, A3, A4 and A7) cause competitive inhibition and compounds (A5, A6 and A8) cause mixed type of inhibition.