Marmara Pharmaceutical Journal 2017 , Vol 21 , Issue 4
Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators
Leyla YURTTAŞ1,Kaan KÜÇÜKOĞLU2,Hayrünnisa NADAROĞLU3,Zafer Asım KAPLANCIKLI1
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bülent Ecevit University, Zonguldak, Turkey
3Department of Food Technology, Erzurum Vocational Training School, Ataturk University, 25240 Erzurum, Turkey
DOI : 10.12991/mpj.2017.19 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