Phenylsulfonylpiperazines as α-Glucosidase Enzyme Inhibitors: Design, Synthesis, DFT Calculations, Docking and ADME Studies

Yıl 2024, Cilt: 13 Sayı: 3, 723 - 730, 26.09.2024

Kerem Buran , Yiğit İnan , Gülşah Selin Akyüz , Celile Dervişoğlu Özdemir , Fatih Kocabas

https://doi.org/10.17798/bitlisfen.1479292

Öz

Diabetes Mellitus (DM), tüm dünyada insanları etkileyen en yaygın hastalıklardan biridir. Kandaki düşük insülin seviyeleri ve yüksek glikoz seviyeleri ile karakterizedir. DM'nin önemli bir tedavisi a-glikosidaz enziminin inhibisyonudur. Piperazin ve sülfonamid yapılarının çeşitli biyolojik aktiviteleri bilinmektedir. Bu çalışmada beş adet fenilsülfonil piperazin türevi sentezlenip enzim inhibisyon kapasiteleri değerlendirildi. Sentezlenen moleküller (1-5), a-glukosidaz enziminin iyi derecede inhibe ettiği görüldü. Bileşik 1, a-glukosidaz enzimi için en yüksek inhibisyon potansiyeline sahiptir. İnhibisyon yüzdesi (83,52±0,41), referans molekül olan quercetine (81,41±0,02) göre daha yüksektir. Olası protein-ligand etkileşimlerini belirlemek amacıyla a-glukosidaz enzimi için en güçlü bileşik 1 için silico moleküler yerleştirme çalışmaları yapıldı. Ayrıca kuantum mekanik ve elektronik özelliklerinin değerlendirilmesi için bir DFT çalışması yapılmıştır. Son olarak bileşiklerin ADME profilleri teorik olarak analiz edildi.

Anahtar Kelimeler

Diabetes mellitus, α-Glucosidase, Sulfonamide, Piperazine, DFT calculations

Etik Beyan

The study is complied with research and publication ethics.

Proje Numarası

2020/040

Teşekkür

This project was supported by the University of Health Sciences, unit of scientific research project (BAP) (Project No:2020/040). The Gaussian calculations made in the article were made in the Marmara University Computational Chemistry Laboratory. We would like to thank Safiye Sağ Erdem for her support.

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