A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants

Abstract

In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC 50 values of 0.15 0.01, 0.086 0.01 and 0.32 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-αglucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.

Synthesis, Structure Elucidation and Biological Activity of New Hybrid Hydrazone-Amide Compounds

“…4-Aminosalicylic acid (4-ASA) was chosen as a starting compound for this study. Its ester and hydrazide derivatives were synthesized accordingly; confirming with the literature data [11,12]. The corresponding hydrazide derivatives were then converted into their hydrazidehydrazone structures.…”

“…The mixture was heated under reflux for 20-24 h and the reaction was monitored with TLC. After the reaction was completed, the mixture was neutralized with 10% NaHCO 3 and the solid obtained was filtered and recrystallized with ethanol [11].…”

N-Hydroxy-N-Propargylamide Derivatives of Ferulic Acid: Inhibitors of Cholinesterases and Monoamine Oxidases

“…The synthesis of the new FA derivatives 1 – 6 was carried out in short synthetic procedures, as shown in Scheme 1 , Scheme 2 , Scheme 3 and Scheme 4 , in good overall yields, starting from readily available precursors. As shown in Scheme 1 and as previously described [ 22 ], the reaction of FA with MeOH catalyzed with concentrated sulfuric(VI) acid gave ester 7 in quantitative yield, which after standard O -alkylation with commercial 1-(2-chloroethyl)piperidine hydrochloride gave ether 8 in 86% yield. Reaction of ether 8 with aqueous hydroxylamine in basic medium gave the target ligand 1 in a modest, unoptimized yield of 30%.…”

“…Methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate ( 7 ) [ 22 ]. To a solution of ferulic acid (10.0 g, 51.5 mmol) in MeOH (30 mL), cc H 2 SO 4 (1.3 mL) was added.…”

Efficient Synthesis of Hydroxy-Substituted 2-Aminobenzo[d]thiazole-6-carboxylic Acid Derivatives as New Building Blocks in Drug Discovery

“…1 H NMR (400 MHz, DMSO-d 6 ): δ 3.66 (s, 3H), 3.71 (s, 3H), 5.94 (s, 2H), 6.14 (dd, J = 8.5, 2.0 Hz, 1H), 6.20 (d, J = 2.0 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H).4.2.5.4. Methyl 4-Amino-2-(benzyloxy)benzoate (10b) 35. Compound 9b (0.605 g, 1.69 mmol) was dissolved in 2 M HCl in diethyl ether (5 mL) and stirred at rt for 15 h. The precipitate in the reaction mixture was filtered off and suspended in ethyl acetate (50 mL) which was washed with saturated aqueous NaHCO 3 solution (30 mL) and brine (30 mL), dried over Na 2 SO 4 , filtered, and the solvent was removed in vacuo.…”