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

Sevil Şenkardeş; Zeynep Hanne Baş

Article Details

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

Authors:

Sevil Şenkardeş | Zeynep Hanne Baş

Publisher:

Van Yuzuncu Yıl University

Main Topics:

Organik Kimyasal Sentez

Journal:

Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.30 Issue 1, pp.69-77

Document Type:

Article

Publication Date:

4/2025

Document Language:

English

Document ID (Org No.):

2001344506

pISSN:

1300-5413

Keywords:

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-trifluoromethylanilinobenzoylhydrazine-1-carboxylate compound 3d, an etofenamate derivative, revealed the highest inhibitory potential with IC50 values of 188.300.1 μg mL-1 when compared with standard acarbose having IC50 value 190.702.05 μg mL-1. These findings highlight the potential of NSAID-linked hydrazide derivatives as promising candidates for the development of novel DM therapies.

 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-trifluoromethylanilinobenzoylhydrazine-1-carboxylate compound 3d, an etofenamate derivative, revealed the highest inhibitory potential with IC50 values of 188.300.1 μg mL-1 when compared with standard acarbose having IC50 value 190.702.05 μg mL-1. These findings highlight the potential of NSAID-linked hydrazide derivatives as promising candidates for the development of novel DM therapies.

 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-trifluoromethylanilinobenzoylhydrazine-1-carboxylate compound 3d, an etofenamate derivative, revealed the highest inhibitory potential with IC50 values of 188.300.1 μg mL-1 when compared with standard acarbose having IC50 value 190.702.05 μg mL-1. These findings highlight the potential of NSAID-linked hydrazide derivatives as promising candidates for the development of novel DM therapies.

 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. DMnin 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-triflorometilanilinobenzoilhidrazin-1-karboksilat bileşik 3d, 190.702.05 μg ml-1 IC50 değerine sahip standart akarbozla karşılaştırıldığında 188.300.1 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.

Article Details

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

Authors:

Sevil Şenkardeş | Zeynep Hanne Baş

Publisher:

Van Yuzuncu Yıl University

Main Topics:

Organik Kimyasal Sentez

Journal:

Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.30 Issue 1, pp.69-77

Document Type:

Article

Publication Date:

4/2025

Document Language:

English

Document ID (Org No.):

2001344506

pISSN:

1300-5413

Carboxylate

Diabetes Mellitus

Glucosidase

Hydrazide

NSAIDDiabetes Mellitus

Glukosidaz

Hidrazid

Karboksilat

NSAİİ

Issues

Article Details

Authors: Sevil Şenkardeş | Zeynep Hanne Baş

Publisher: Van Yuzuncu Yıl University

Main Topics: Organik Kimyasal Sentez

Journal: Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.30 Issue 1, pp.69-77

Document Type: Article

Publication Date: 4/2025

Document Language: English

Document ID (Org No.): 2001344506

pISSN: 1300-5413

Issues

Authors:

Sevil Şenkardeş | Zeynep Hanne Baş

Publisher:

Van Yuzuncu Yıl University

Main Topics:

Organik Kimyasal Sentez

Journal:

Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.30 Issue 1, pp.69-77

Document Type:

Article

Publication Date:

4/2025

Document Language:

English

Document ID (Org No.):

2001344506

pISSN:

1300-5413