Potential inhibitors of human carbonic anhydrase isozymes I and II: Design, synthesis and docking studies of new 1,3,4-thiadiazole derivatives

In the last years, inhibition of carbonic anhydrase (CA) has emerged as a promising approach for pharmacologic intervention in a variety of disorders such as glaucoma, epilepsy, obesity, and cancer. As a consequence, the design of CA inhibitors (CAIs) is a highly dynamic field of medicinal chemistry. Due to the therapeutic potential of thiadiazoles as CAIs, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their inhibitory effects on hCA I and hCA II. Although the tested compounds did not carry a sulfonamide group, an important pharmacophore for CA inhibitory activity, it was a remarkable finding that most of them were more effective on hCAs than acetazolamide (AAZ), the reference agent. Among these compounds, N'-((5-(4-chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)thio)acetohydrazide (3) was found to be the most effective compound on hCA I with an IC50 value of 0.14 nM, whereas N'-((5-(2-chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)thio)acetohydrazide (1) was found to be the most potent compound on hCA II with an IC50 value of 0.15 nM. According to molecular docking studies, all compounds exhibited high affinity and good amino acid interactions similar to AAZ on the both active sites of hCA I and hCA II enzymes. © 2017 Elsevier Ltd

Yazar Altıntop M.D.
Sever B.
Özdemir A.
Kucukoglu K.
Onem H.
Nadaroglu H.
Kaplancıklı Z.A.
Yayın Türü Article
Tek Biçim Adres https://hdl.handle.net/20.500.12628/7090
Tek Biçim Adres 10.1016/j.bmc.2017.05.005
Konu Başlıkları Carbonic anhydrase
Furan
Hydrazone
Molecular docking
Thiadiazole
Koleksiyonlar Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed | SOBİAD
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu
Dergi Adı Bioorganic and Medicinal Chemistry
Dergi Cilt Bilgisi 25
Dergi Sayısı 13
Sayfalar 3547 - 3554
Yayın Yılı 2017
Eser Adı
[dc.title]
Potential inhibitors of human carbonic anhydrase isozymes I and II: Design, synthesis and docking studies of new 1,3,4-thiadiazole derivatives
Yazar
[dc.contributor.author]
Altıntop M.D.
Yazar
[dc.contributor.author]
Sever B.
Yazar
[dc.contributor.author]
Özdemir A.
Yazar
[dc.contributor.author]
Kucukoglu K.
Yazar
[dc.contributor.author]
Onem H.
Yazar
[dc.contributor.author]
Nadaroglu H.
Yazar
[dc.contributor.author]
Kaplancıklı Z.A.
Yayın Yılı
[dc.date.issued]
2017
Yayıncı
[dc.publisher]
Elsevier Ltd
Yayın Türü
[dc.type]
article
Özet
[dc.description.abstract]
In the last years, inhibition of carbonic anhydrase (CA) has emerged as a promising approach for pharmacologic intervention in a variety of disorders such as glaucoma, epilepsy, obesity, and cancer. As a consequence, the design of CA inhibitors (CAIs) is a highly dynamic field of medicinal chemistry. Due to the therapeutic potential of thiadiazoles as CAIs, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their inhibitory effects on hCA I and hCA II. Although the tested compounds did not carry a sulfonamide group, an important pharmacophore for CA inhibitory activity, it was a remarkable finding that most of them were more effective on hCAs than acetazolamide (AAZ), the reference agent. Among these compounds, N'-((5-(4-chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)thio)acetohydrazide (3) was found to be the most effective compound on hCA I with an IC50 value of 0.14 nM, whereas N'-((5-(2-chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)thio)acetohydrazide (1) was found to be the most potent compound on hCA II with an IC50 value of 0.15 nM. According to molecular docking studies, all compounds exhibited high affinity and good amino acid interactions similar to AAZ on the both active sites of hCA I and hCA II enzymes. © 2017 Elsevier Ltd
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]
Carbonic anhydrase
Konu Başlıkları
[dc.subject]
Furan
Konu Başlıkları
[dc.subject]
Hydrazone
Konu Başlıkları
[dc.subject]
Molecular docking
Konu Başlıkları
[dc.subject]
Thiadiazole
Haklar
[dc.rights]
info:eu-repo/semantics/closedAccess
ISSN
[dc.identifier.issn]
0968-0896
Sponsor YAYINCI
[dc.description.sponsorship]
Firat University Scientific Research Projects Management Unit: 1605S318
Sponsor YAYINCI
[dc.description.sponsorship]
This study was supported by Anadolu University Scientific Research Projects Commission under the grant no: 1605S318.
İlk Sayfa Sayısı
[dc.identifier.startpage]
3547
Son Sayfa Sayısı
[dc.identifier.endpage]
3554
Dergi Adı
[dc.relation.journal]
Bioorganic and Medicinal Chemistry
Dergi Sayısı
[dc.identifier.issue]
13
Dergi Cilt Bilgisi
[dc.identifier.volume]
25
Tek Biçim Adres
[dc.identifier.uri]
https://dx.doi.org/10.1016/j.bmc.2017.05.005
Tek Biçim Adres
[dc.identifier.uri]
https://hdl.handle.net/20.500.12628/7090
Görüntülenme Sayısı ( Şehir )
Görüntülenme Sayısı ( Ülke )
Görüntülenme Sayısı ( Zaman Dağılımı )
Görüntülenme
8
09.12.2022 tarihinden bu yana
İndirme
1
09.12.2022 tarihinden bu yana
Son Erişim Tarihi
09 Şubat 2024 18:14
Google Kontrol
Tıklayınız
compounds 4-thiadiazol-2-yl)thio)acetohydrazide compound inhibitory effective finding reference acetazolamide -((5-(4-chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1 Elsevier enzymes active similar interactions affinity 14 nM exhibited studies docking molecular According 15 nM potent -((5-(2-chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1 whereas remarkable inhibitors design consequence cancer obesity epilepsy glaucoma disorders variety
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