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

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. © 2017, Marmara University. All rights reserved.

Yazar Yurttaş L.
Küçükoğlu K.
Nadaroğlu H.
Kaplancikli Z.A.
Yayın Türü Article
Tek Biçim Adres https://hdl.handle.net/20.500.12628/7753
Tek Biçim Adres 10.12991/mpj.2017.19
Konu Başlıkları Antioxidant defence
Oxidative stress
Paraoxonase (PON1)
Thioacetamide
Triazole
Koleksiyonlar Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed | SOBİAD
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu
Dergi Adı Marmara Pharmaceutical Journal
Dergi Cilt Bilgisi 21
Dergi Sayısı 4
Sayfalar 967 - 977
Yayın Yılı 2017
Eser Adı
[dc.title]
Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators
Yazar
[dc.contributor.author]
Yurttaş L.
Yazar
[dc.contributor.author]
Küçükoğlu K.
Yazar
[dc.contributor.author]
Nadaroğlu H.
Yazar
[dc.contributor.author]
Kaplancikli Z.A.
Yayın Yılı
[dc.date.issued]
2017
Yayıncı
[dc.publisher]
Marmara University
Yayın Türü
[dc.type]
article
Özet
[dc.description.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. © 2017, Marmara University. All rights reserved.
Kayıt Giriş Tarihi
[dc.date.accessioned]
2019-12-23
Açık Erişim Tarihi
[dc.date.available]
2019-12-23
Yayın Dili
[dc.language.iso]
eng
Konu Başlıkları
[dc.subject]
Antioxidant defence
Konu Başlıkları
[dc.subject]
Oxidative stress
Konu Başlıkları
[dc.subject]
Paraoxonase (PON1)
Konu Başlıkları
[dc.subject]
Thioacetamide
Konu Başlıkları
[dc.subject]
Triazole
Haklar
[dc.rights]
info:eu-repo/semantics/openAccess
ISSN
[dc.identifier.issn]
1309-0801
İlk Sayfa Sayısı
[dc.identifier.startpage]
967
Son Sayfa Sayısı
[dc.identifier.endpage]
977
Dergi Adı
[dc.relation.journal]
Marmara Pharmaceutical Journal
Dergi Sayısı
[dc.identifier.issue]
4
Dergi Cilt Bilgisi
[dc.identifier.volume]
21
Tek Biçim Adres
[dc.identifier.uri]
https://dx.doi.org/10.12991/mpj.2017.19
Tek Biçim Adres
[dc.identifier.uri]
https://hdl.handle.net/20.500.12628/7753
Görüntülenme Sayısı ( Şehir )
Görüntülenme Sayısı ( Ülke )
Görüntülenme Sayısı ( Zaman Dağılımı )
Görüntülenme
12
09.12.2022 tarihinden bu yana
İndirme
1
09.12.2022 tarihinden bu yana
Son Erişim Tarihi
10 Şubat 2024 00:09
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Tıklayınız
compounds enzyme activity further disease triazole lipoprotein purified bearing levels candidate synthesized Sepharose (5a-i) moiety method precipitation thioacetamide sulfate 4B-L-tyrosine- investigated ammonium Coronary 1-naphthylamine proceed reserved rights University Marmara investigations considered affinity moieties 6-florobenzothiazole 6-ethoxybenzothiazole
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