Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators

Year 2017, Volume: 21 Issue: 4, 967 - 977, 01.12.2017

Leyla Yurttaş Kaan Küçükoğlu Hayrünnisa Nadaroğlu Zafer Asım Kaplancıklı

Abstract

Coronary artery disease and low-density lipoprotein (LDL)

levels in the blood have long been known to be associated with

peripheral vascular diseases. Paraoxonase-1 (PON1) enzyme is

related to serum levels of high-density lipoprotein (HDL) and

protects LDL from oxidation which may result in development

of microvascular disease in diabetes. The enzyme has a major

role in the prevention of atherosclerosis besides antioxidant

properties. Additionally, PON1 is important in the detoxification

of organophosphate insecticides from the body. In this study, we

aimed to synthesize highly active new compounds which can be a

drug candidate and evaluate their effects on PON1 activity.

Nine novel triazole compounds bearing thioacetamide moiety

(5a-i) were synthesized and their in vitro PON1 activity was

investigated. The PON1 enzyme was purified from human

serum using ammonium sulfate precipitation method. Also,

it was further purified using Sepharose 4B-L-tyrosine-

1-naphthylamine affinity chromatography. Among the

synthesized triazole compounds, 5b, 5c, 5f and 5h have been

determined to increase PON1 activity, remarkably. Compounds

5b, 5c, 5f and 5h bearing 5-nitrothiazole, benzothiazole,

6-ethoxybenzothiazole and 6-florobenzothiazole moieties

could be considered to proceed in vivo investigations which is a

further stage for a drug candidate.

Keywords

Triazole; thioacetamide; paraoxonase (PON1); oxidative stress; antioxidant defence

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