j. inst. sci. and tech.

Journal of the Institute of Science and Technology

2536-4618

Igdir University

10.21597/jist.1687595

Molecular Medicine

Moleküler İlaç

Karboksilik Asit Bağlantılı Tiyazol Türevlerinin Laktoperoksidaz Enzimi Üzerindeki Etkilerinin Araştırılması

Investigation of the Effects of Carboxylic Acid-Linked Thiazole Derivatives on the Lactoperoxidase EnzymeI

https://orcid.org/0000-0001-7699-1697

Gerni

Serpil

Atatürk Üniversitesi

12 01 2025

15 4 1472 1479 04 30 2025 07 01 2025

2011

Journal of the Institute of Science and Technology

Bu çalışmada, karboksilik asit fonksiyonel grubuna sahip tiyazol türevlerinin Laktoperoksidaz (LPO) enzimi üzerindeki inhibitör etkileri detaylı olarak incelenmiştir. Enzim saflaştırma işlemi, sığır sütünden elde edilen LPO’nun Sepharose 4B-L-tirozin-sülfanilamid afinite kolon kromatografisi ile başarılı bir şekilde izole edilmesiyle gerçekleştirilmiştir. İnhibisyon çalışmalarında substrat olarak 2,2'-azino-bis(3-etilbenzotiyazolin-6-sülfonik asit) (ABTS) kullanılmış ve elde edilen kinetik veriler doğrultusunda, karboksilik asit içeren tiyazol türevlerinin LPO enzim aktivitesini etkili biçimde inhibe ettiği belirlenmiştir. Test edilen beş farklı tiyazol türevinin inhibisyon parametreleri değerlendirilmiş; bileşiklerin Ki değerleri sırasıyla 1.734 ± 0.810 µM, 1.988 ± 0.934 µM, 1.226 ± 0.148 µM, 1.128 ± 0.053 µM ve 3.818 ± 0.264 µM olarak saptanmıştır. Yapılan inhibitör tip analizleri sonucunda yalnızca 2-bromo-tiyazol-5-karboksilik asidin (a) yarışmalı (kompetitif) inhibisyon mekanizması gösterdiği, diğer dört bileşiğin ise yarışmasız (nonkompetitif) inhibitör olarak davrandığı belirlenmiştir. Özellikle tiyazol-5-karboksilik asit türevi (d), 1.128 ± 0.053 µM’lik en düşük Ki değeri ve 2.840 µM’lik IC₅₀ değeri ile çalışmada en güçlü inhibitör etkiyi gösteren bileşik olmuştur. Bu sonuç, söz konusu bileşiğin LPO enzimi için potansiyel bir inhibitör aday olarak değerlendirilmesine olanak sağlamaktadır.

In this study, the inhibitory effects of thiazole derivatives containing a carboxylic acid functional group on the lactoperoxidase (LPO) enzyme were investigated in detail. LPO was successfully purified from bovine milk using Sepharose 4 B-L-tyrosine-sulfanilamide affinity column chromatography. In the inhibition studies, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was used as the substrate. Based on the obtained kinetic data, it was determined that thiazole derivatives bearing a carboxylic acid group effectively inhibited LPO enzyme activity. The inhibition parameters of five different thiazole derivatives were evaluated, and their Ki values were determined as 1.734 ± 0.810 µM, 1.988 ± 0.934 µM, 1.226 ± 0.148 µM, 1.128 ± 0.053 µM, and 3.818 ± 0.264 µM, respectively. Inhibitor type analyses revealed that only 2-bromothiazole-5-carboxylic acid (a) exhibited a competitive inhibition mechanism, while the remaining four compounds acted as non-competitive inhibitors. Notably, the thiazole-5-carboxylic acid derivative (d) demonstrated the strongest inhibitory effect in the study, with the lowest Ki value of 1.128 ± 0.053 µM and an IC₅₀ value of 2.840 µM. These results suggest that this compound may serve as a promising inhibitor candidate for the LPO enzyme.

Laktoperoksidaz Tiyazol türevleri İnhibisyon • Sığır Sütü

• Lactoperoxidase • ThiazoleDerivatives • Inhibition • Bovine Milk

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