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

Year 2024, Volume: 13 Issue: 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

Abstract

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.

Keywords

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

Ethical Statement

The study is complied with research and publication ethics.

Project Number

2020/040

Thanks

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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