j res pharm Marmara Pharmaceutical Journal 1309-0801 Marmara University Health Care Administration Sağlık Kurumları Yönetimi Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators Yurttaş Leyla Küçükoğlu Kaan Nadaroğlu Hayrünnisa Kaplancıklı Zafer Asım 12 01 2017 21 4 967 977 05 08 2017 06 23 2017 Copyright © 1985, Marmara Pharmaceutical Journal 1985 Marmara Pharmaceutical Journal

Coronary artery disease and low-density lipoprotein (LDL)levels in the blood have long been known to be associated withperipheral vascular diseases. Paraoxonase-1 (PON1) enzyme isrelated to serum levels of high-density lipoprotein (HDL) andprotects LDL from oxidation which may result in developmentof microvascular disease in diabetes. The enzyme has a majorrole in the prevention of atherosclerosis besides antioxidantproperties. Additionally, PON1 is important in the detoxificationof organophosphate insecticides from the body. In this study, weaimed to synthesize highly active new compounds which can be adrug 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 wasinvestigated. The PON1 enzyme was purified from humanserum using ammonium sulfate precipitation method. Also,it was further purified using Sepharose 4B-L-tyrosine-1-naphthylamine affinity chromatography. Among thesynthesized triazole compounds, 5b, 5c, 5f and 5h have beendetermined to increase PON1 activity, remarkably. Compounds5b, 5c, 5f and 5h bearing 5-nitrothiazole, benzothiazole,6-ethoxybenzothiazole and 6-florobenzothiazole moietiescould be considered to proceed in vivo investigations which is afurther stage for a drug candidate.

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