Classical and Variant Approaches to Synthesis of N-Mannich Bases of Phenyl Hydroxyl Ketones, Their Characterization, Urease Inhibition and Antioxidant Activities

Abstract

In continuation of our synthesis and investigation of bioactivities of Mannich bases, synthesized N - Mannich bases were evaluated for their urease inhibition and antioxidant properties. Characterization was achieved by Ultraviolet/visible (UV), Infrared (IR), Nuclear magnetic resonance (¹HNMR) and Mass spectrophotometries. Elemental analysis, optical rotation (OR) and circular dichroism (CD) measurement also confirmed and provided information about the structure of these compounds. Synthesis of novel 2-hydroxy-1,2,3-triphenyl-3-(phenylamino) propan-1-one, 2-hydroxy-1,2-diphenyl-3-(phenylamino) propan-1-one, 2-hydroxy-3-(2-hydroxyethylamino)-1,2,3-triphenylpropan-1-one and  2-hydroxy-1,2,3-triphenyl-3-(p-tolylamino)propan-1-one are newly reported along with 3-(2-(3,4-dimethoxyphenyl)ethylideneamino)-3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxy phenyl) propan-1-one prepared by a variant approach involving use of tertiary amine. Jack bean Urease was used for Urease inhibition assay while in vitro antioxidant screening of the compounds was carried out using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH).  IC₅₀ values obtained showed that the compounds showed significant activities as urease inhibitors and antioxidants when compared with Thiourea, Ascorbic acid and Butylated hydroxyanisole (BHA) used as standards in the two assays. Kinetics of inhibition of H. pylori urease by 1-Phenylaminomethyl-naphthalen-2-ol (GK1) and 2-(3-Phenylaminopropionyloxy)-benzoic acid (GK5) indicated that enzyme activity decreased as concentration of test compound increased. The IC₅₀ value of 14.5 ± 0.71 mM (GK1)  and 14.3± 0.32 (GK5) indicated better activity when compared to thiourea (21.6 ± 0.12) used as standard.

Keywords: Benzoin; tertiary amine; urease; thiourea; antioxidant; butylated hydroxyanisole