Synthesis, Enzyme Inhibition, and Acid Dissociation Constant of 1,4-Naphthoquinone Thiazole Hybrid

Year 2024, Volume: 44 Issue: 3, 234 - 243, 01.09.2024

Yahya Nural , Yeliz Demir

https://doi.org/10.52794/hujpharm.1432876

Abstract

In this study, N-((Z)-4-((3r,5r,7r)-adamantan-1-yl)-3-(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2yl)thiazol-2(3H)-ylidene)-2,6-difluorobenzamide 3 was synthesized as a new 1,4-naphthoquinone thiazole hybrid compound by reaction of naphthoquinone acyl thiourea compound 2 with 1-((3r,5r,7r)-adamantan-1-yl)-2-bromoethan-1-one in 74% yield and its molecular structure was characterized by various analytical techniques such as 1H/13C NMR, FT-IR, and HRMS. The inhibition effect of the synthesized compound on butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoenzymes (hCA I and hCA II) was investigated. The product 3 showed varying degrees of inhibition 89.92 ± 10.47 nM (against hCA I), 51.60 ± 5.37 nM (against hCA II), 68.11 ± 6.58 nM (against AChE), and 126.90 ± 10.99 (against BChE). Although 1,4-naphthoquinone thiazole hybrid 3 showed significant enzyme activity against the enzymes tested, it showed a higher inhibition activity against the AChE enzyme than the standard drug Tacrine. Three acid dissociation constants (pKa) values (pKa1= 2.75±0.02, pKa2= 6.79±0.02, pKa3= 10.85±0.02) of the product were determined potentiometrically in 0.1 M NaCl ionic strength at 25.0±0.1 ºC in 25% (v/v) DMSO:water hydro organic medium.

Keywords

Thiazole, Enzyme inhibition, Acid dissociation constant, 1, 4-Naphthoquinone

1,4-Naftokinon Tiyazol Hibritinin Sentezi, Enzim İnhibisyonu ve Asit Ayrışma Sabiti

Abstract

Bu çalışmada, yeni naftokinon tiyazol hibriti 3 1-((3r,5r,7r)-adamantan-1-il)-2-bromoetan-1-on ile naftokinon açil tiyoüre bileşiğinin 2 tepkimesi ile 74% verimle sentezlendi ve moleküler yapısı çeşitli analitik tekniklerle karakterize edildi. Sentezlenen bileşiğin bütirilkolinesteraz (BChE), asetilkolinesteraz (AChE) ve insan karbonik anhidraz izoenzimleri (hCA I ve hCA II) üzerindeki inhibisyon etkisi araştırıldı. Ürün 3, 89,92 ± 10,47 nM (hCA I'e karşı), 51,60 ± 5,37 nM (hCA II'ye karşı), 68,11 ± 6,58 nM (AChE'ye karşı) ve 126,90 ± 10,99 (BChE'ye karşı) gibi değişen değerlerde inhibisyon gösterdi. Ürünün üç asit dissosiyasyon sabiti (pKa) değeri (pKa1= 2,75±0,02, pKa2= 6,79±0,02, pKa3= 10,85±0,02) belirlendi.

Keywords

1,4-Naftokinon, Tiyazol, Enzim inhibisyonu, Asit dissosiyasyon sabiti

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