Aldose Reductase Evaluation against Diabetic Complications Using ADME and Molecular Docking Studies and DFT Calculations of Spiroindoline Derivative Molecule

Year 2024, , 281 - 292, 23.08.2024

Kenan Gören , Ümit Yıldıko

https://doi.org/10.19113/sdufenbed.1474689

Abstract

In this study, the target molecule ethyl-2-(5-nitro-5'-(4-nitrophenyl)-2-oxo-3'H-spiro[indoline-3,2'-[1,3,4]oxadiazol]-1-yl)acetate, which is a spiroindoline derivative, were performed NBO analysis, molecular electrostatic potential surface (MEPS), nonlinear optics (NLO), HOMO-LUMO energy calculations, optimized molecular geometry, and mulliken atomic charges using B3LYP/B3PW91 basis set and 6-311G(d,p) approximations. Calculated results were reported. Density Functional Theory (DFT) computations were utilized to research the molecule theoretically. Moreover, molecular docking analysis of the tested compound, a spiroindoline derivative molecule targeting aldose reductase against diabetic complications, was performed using molecular docking to determine the structure-activity connection. The molecular docking study provided important information worth considering for further research. A notable outcome of bioisosteric and isosteric substitutions is the alteration in lipophilic character, an impressive characteristic in several aspects. Thus, utilizing SwissADME, lipophilic character assessments were performed for the concerned compounds.

Keywords

Spiroindoline Derivative, DFT, Molecular Docking, MEP, ADME, NBO.

Spiroindolin Türevi Molekülünün DFT Hesaplamaları ve ADME ve Moleküler Doking Çalışmaları Kullanılarak Diyabetik Komplikasyonlara Karşı Aldoz Redüktaz Değerlendirmesi

Abstract

Bu çalışmada, spiroindolin türevi olan, hedef molekül etil-2-(5-nitro-5'-(4-nitrofenil)-2-okso-3'H-spiro[indolin-3,2'-[1,3,4]oksadiazol]-1-il)asetat’in B3PW91/B3LYP temel set ve 6-311G(d,p) yaklaşımlar kullanılarak NBO analizi, moleküler elektrostatik potansiyel yüzey (MEPS), HOMO-LUMO enerji hesaplamaları, doğrusal olmayan optik (NLO), optimize edilmiş moleküler geometri ve mulliken atomik yükleri hesaplamaları yapıldı. Hesaplanan sonuçlar açıklandı. Molekülün teorik olarak incelenmesi için Yoğunluk Fonksiyonel Teorisi (DFT) hesaplamaları kullanıldı. Ayrıca, diyabet komplikasyonlarına karşı aldoz redüktazı hedef alan spiroindolin türevi molekülü olan test edilen bileşiğin yapı-aktivite bağlantısını belirlemek amacıyla moleküler docking analizi yapıldı. Moleküler doking çalışması, ileri araştırmalar için dikkate değer önemli bilgiler sağladı. Biyoizosterik ve izosterik yer değiştirmelerin dikkate değer bir sonucu, çeşitli yönlerden etkileyici bir özellik olan lipofilik karakterdeki değişikliktir. Bu yüzden SwissADME kullanılarak söz konusu bileşikler için lipofilik karakter değerlendirmeleri yapılmıştır.

Keywords

Spiroindolin Türe, DFT, Molecular Doking, MEP, ADME, NBO.

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