In silico Molecular Docking and ADME Studies of 1 3,4-Thiadiazole Derivatives in Relation to in vitro PON1 Activity

Background: Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. Objective: Based on antioxidative properties of PON1 and significance of 1,3,4-thiadiazoles in pharmaceutical chemistry, herein we aimed to evaluate the potentials of 1,3,4-thiadiazole derivatives as PON1 activators. Methods: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]acetophenone derivatives (1-18) were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography. Molecular docking studies were performed for the detection of affinities of all compounds to the active site of PON1. Moreover, Absorption, Distribution, Metabolism and Excretion (ADME) properties of all compounds were also in silico predicted. In silico molecular docking and ADME studies were carried out according to modules of Schrodinger's Maestro molecular modeling package. Results: All compounds, particularly compounds 10, 13 and 17, were determined as promising PON1 activators and apart from compound 1, all of them were detected in the active site of PON1. Besides, ADME results indicated that all compounds were potential orally bioavailable drug-like molecules. Conclusion: PON1 activators, compounds 10, 13 and 17 stand out as potential drug candidates for further antioxidant studies and these compounds can be investigated for their therapeutic effects in many disorders such as atherosclerosis, diabetes mellitus, obesity, chronic liver inflammation and many more.

Yazar Sever, Belgin
Kucukoglu, Kaan
Nadaroglu, Hayrunnisa
Altintop, Mehlika Dilek
Yayın Türü Article
Tek Biçim Adres https://hdl.handle.net/20.500.12628/2762
Tek Biçim Adres 10.2174/1573409914666180518085908
Konu Başlıkları Paraoxonase 1
thiadiazole
molecular docking
ADME
antioxidant activity
PON1 activators
Koleksiyonlar Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed | SOBİAD
PubMed İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu
Dergi Adı CURRENT COMPUTER-AIDED DRUG DESIGN
Dergi Cilt Bilgisi 15
Dergi Sayısı 2
Sayfalar 136 - 144
Yayın Yılı 2019
Eser Adı
[dc.title]
In silico Molecular Docking and ADME Studies of 1 3,4-Thiadiazole Derivatives in Relation to in vitro PON1 Activity
Yazar
[dc.contributor.author]
Sever, Belgin
Yazar
[dc.contributor.author]
Kucukoglu, Kaan
Yazar
[dc.contributor.author]
Nadaroglu, Hayrunnisa
Yazar
[dc.contributor.author]
Altintop, Mehlika Dilek
Yayın Yılı
[dc.date.issued]
2019
Yayıncı
[dc.publisher]
BENTHAM SCIENCE PUBL LTD
Yayın Türü
[dc.type]
article
Özet
[dc.description.abstract]
Background: Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. Objective: Based on antioxidative properties of PON1 and significance of 1,3,4-thiadiazoles in pharmaceutical chemistry, herein we aimed to evaluate the potentials of 1,3,4-thiadiazole derivatives as PON1 activators. Methods: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]acetophenone derivatives (1-18) were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography. Molecular docking studies were performed for the detection of affinities of all compounds to the active site of PON1. Moreover, Absorption, Distribution, Metabolism and Excretion (ADME) properties of all compounds were also in silico predicted. In silico molecular docking and ADME studies were carried out according to modules of Schrodinger's Maestro molecular modeling package. Results: All compounds, particularly compounds 10, 13 and 17, were determined as promising PON1 activators and apart from compound 1, all of them were detected in the active site of PON1. Besides, ADME results indicated that all compounds were potential orally bioavailable drug-like molecules. Conclusion: PON1 activators, compounds 10, 13 and 17 stand out as potential drug candidates for further antioxidant studies and these compounds can be investigated for their therapeutic effects in many disorders such as atherosclerosis, diabetes mellitus, obesity, chronic liver inflammation and many more.
Açıklama
[dc.description]
WOS: 000460882500003
Açıklama
[dc.description]
PubMed: 29773067
Kayıt Giriş Tarihi
[dc.date.accessioned]
2019-12-23
Açık Erişim Tarihi
[dc.date.available]
2019-12-23
Yayın Dili
[dc.language.iso]
eng
Konu Başlıkları
[dc.subject]
Paraoxonase 1
Konu Başlıkları
[dc.subject]
thiadiazole
Konu Başlıkları
[dc.subject]
molecular docking
Konu Başlıkları
[dc.subject]
ADME
Konu Başlıkları
[dc.subject]
antioxidant activity
Konu Başlıkları
[dc.subject]
PON1 activators
Haklar
[dc.rights]
info:eu-repo/semantics/closedAccess
ISSN
[dc.identifier.issn]
1573-4099
ISSN
[dc.identifier.issn]
1875-6697
İlk Sayfa Sayısı
[dc.identifier.startpage]
136
Son Sayfa Sayısı
[dc.identifier.endpage]
144
Dergi Adı
[dc.relation.journal]
CURRENT COMPUTER-AIDED DRUG DESIGN
Dergi Sayısı
[dc.identifier.issue]
2
Dergi Cilt Bilgisi
[dc.identifier.volume]
15
Tek Biçim Adres
[dc.identifier.uri]
https://dx.doi.org/10.2174/1573409914666180518085908
Tek Biçim Adres
[dc.identifier.uri]
https://hdl.handle.net/20.500.12628/2762
Görüntülenme Sayısı ( Şehir )
Görüntülenme Sayısı ( Ülke )
Görüntülenme Sayısı ( Zaman Dağılımı )
Görüntülenme
6
09.12.2022 tarihinden bu yana
İndirme
1
09.12.2022 tarihinden bu yana
Son Erişim Tarihi
06 Şubat 2024 19:57
Google Kontrol
Tıklayınız
compounds studies activators potential effects properties derivatives docking silico active molecular promising determined modeling particularly Results package Maestro Schrodinger modules according carried Background compound inflammation chronic obesity mellitus diabetes atherosclerosis disorders therapeutic investigated antioxidant further
6698 sayılı Kişisel Verilerin Korunması Kanunu kapsamında yükümlülüklerimiz ve çerez politikamız hakkında bilgi sahibi olmak için alttaki bağlantıyı kullanabilirsiniz.

creativecommons
Bu site altında yer alan tüm kaynaklar Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.
Platforms