Yeni Hidrazid Türevlerinin Sentezi, Yapı Aydınlatma ve -Glukozidaz İnhibitör Etki Çalışmaları

Year 2025, Volume: 30 Issue: 1, 69 - 77, 29.04.2025

Sevil Şenkardeş , Zeynep Hanne Baş

https://doi.org/10.53433/yyufbed.1613136

Abstract

Diabetes Mellitus (DM), dünya çapında 422 milyondan fazla insanı etkileyen kronik ve ilerleyici bir metabolik hastalıktır. Yetersiz insülin üretimi veya hücrelerin insüline yanıt verememesi sonucu ortaya çıkar ve karbonhidrat, yağ ve protein metabolizmasında bozulmalara yol açar. Zamanla DM, kardiyovasküler hastalıklar, böbrek yetmezliği ve görme kaybı gibi ciddi komplikasyonlara neden olabilir. DM'nin etkili yönetimi, kan şekeri seviyelerini stabilize etmeyi amaçlayan terapötik stratejileri içerir. Bunlar arasında, α-glukozidaz enzim inhibitörleri, karbonhidrat sindirimini yavaşlatarak ve yemek sonrası kan şekeri yükselmelerini azaltarak önemli bir rol oynar. Bu çalışmada, steroid olmayan anti-inflamatuar ilaçlarla (NSAII) bağlantılı hidrazid türevleri sentezlenmiş ve potansiyel α-glukozidaz enzim inhibitörleri olarak değerlendirilmiştir. Bu türevlerin yapısal karakterizasyonu, ¹H-NMR, FTIR ve kütle spektrometrisi (MS) gibi teknikler kullanılarak gerçekleştirilmiştir. Bu bileşiklerin tümü, α-glukozidaz enzim inhibisyon aktiviteleri açısından in vitro yöntemle test edilmiştir. Sentezlenen türevler arasında etofenamat türevi olan etil 2-{3-[3-(triflorometil)anilino]benzoil}hidrazin-1-karboksilat (bileşik 3d), 190.70±2.05 μg ml-1 IC50 değerine sahip standart akarbozla karşılaştırıldığında 188.30±0.1 μg ml-1 IC50 değeriyle en yüksek inhibisyon gösteren bileşik olduğu sonucuna varılmıştır. Bu bulgular, NSAII bağlantılı hidrazid türevlerinin yeni DM tedavilerinin geliştirilmesi için umut verici adaylar olabileceğini göstermektedir

Keywords

Diabetes Mellitus , Glukosidaz , Hidrazid , Karboksilat , NSAİİ

Project Number

1919B012324778

Synthesis, Structural Elucidation and α-Glucosidase Inhibitory Activity of New Hydrazide Derivatives

Abstract

Diabetes mellitus (DM) is a chronic and progressive metabolic disorder affecting over 422 million people globally. It arises from insufficient insulin production or the inability of cells to respond to insulin, leading to disruptions in carbohydrate, fat, and protein metabolism. Over time, DM can result in severe complications such as cardiovascular diseases, kidney failure, and vision loss. Effective management of DM includes therapeutic strategies aimed at stabilizing blood glucose levels. Among these, α-glucosidase enzyme inhibitors play a crucial role by slowing carbohydrate digestion and reducing postprandial blood glucose spikes. In this study, new hydrazide derivatives linked to non-steroidal anti-inflammatory drugs (NSAIDs) were synthesized and evaluated as potential α-glucosidase enzyme inhibitors. Structural characterization of these derivatives was performed using techniques such as ¹H-NMR, FTIR, and mass spectrometry (MS). All of these compounds were tested in vitro for their α-glucosidase enzyme inhibition activity. Among the synthesized derivatives, ethyl 2-{3-[3-(trifluoromethyl)anilino]benzoyl}hydrazine-1-carboxylate (compound 3d), an etofenamate derivative, revealed the highest inhibitory potential with IC50 values of 188.30±0.1 μg mL-1 when compared with standard acarbose having IC50 value 190.70±2.05 μg mL-1. These findings highlight the potential of NSAID-linked hydrazide derivatives as promising candidates for the development of novel DM therapies.

Keywords

Carboxylate , Diabetes Mellitus , Glucosidase , Hydrazide , NSAID

Supporting Institution

TUBITAK 2209-A

Project Number

1919B012324778

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