Scopus
YÖKSİS Eşleşti
Synthesis, in silico and in vitro evaluation of new 3,5-disubstituted-1,2,4-oxadiazole derivatives as carbonic anhydrase inhibitors and cytotoxic agents
Journal of Molecular Structure · Mart 2023
YÖKSİS Kayıtları
Synthesis, in silico and in vitro evaluation of new 3,5-disubstituted-1,2,4-oxadiazole derivatives as carbonic anhydrase inhibitors and cytotoxic agents
Journal of Molecular Structure · 2023 SCI-Expanded
PROFESÖR BAHADIR ÖZTÜRK →
Synthesis, in silico and in vitro evaluation of new
3,5-disubstituted-1,2,4-oxadiazole derivatives as carbonic anhydrase
inhibitors and cytotoxic agents
Journal of Molecular Structure · 2023 SCI-Expanded
PROFESÖR KAAN KÜÇÜKOĞLU →
Synthesis, in silico and in vitro evaluation of new 3,5-disubstituted-1,2,4-oxadiazole derivatives as carbonic anhydrase inhibitors and cytotoxic agents
Journal of Molecular Structure · 2023 SCI-Expanded
DOKTOR ÖĞRETİM ÜYESİ NAGİHAN FAYDALI →
Makale Bilgileri
DergiJournal of Molecular Structure
Yayın TarihiMart 2023
Cilt / Sayfa1276
Scopus ID2-s2.0-85144074339
Özet
In this work, new 3,5-disubstituted-1,2,4-oxadiazoles were synthesized efficiently and evaluated for their inhibitory effects on human carbonic anhydrase (hCA) I and II. Most of them were more potent on hCAs than acetazolamide (AAZ). Compounds 10d and 17d were the most potent compounds on hCA I with IC50 values of 0.68 and 0.96 µM, respectively. Compounds 7d, 17d, 10d, and 3d were the most effective hCA II inhibitors with IC50 values of 0.40, 0.40, 0.65 and 0.71 µM. Molecular docking studies revealed that compounds 10d and 17d displayed π-π stacking interactions with Phe91 in the active site of hCA I. Compounds 10d and 17d were capable of forming π-π stacking interaction with His94 and π-cation interaction with Phe131 in the active site of hCA II. The alkylamino groups of both compounds contributed to crucial interactions in the active site of hCA II. Based on in silico data, all compounds were predicted to have good oral bioavailability and drug-likeness. Compounds 10d and 17d can be considered as promising inhibitors of both hCAs. All compounds were examined for their cytotoxicity towards human prostate (DU 145) and breast (MDA-MB-231) cancer cell lines compared to human embryonic kidney 293 cells (HEK-293). The tested compounds showed not only dose- and time-dependent but also cancer cell-specific cytotoxicity. Compounds 6d-11d were the most potent agents on DU 145 cells, whereas the most effective compounds on MDA-MB-231 cells were 6d, 15d-18d. The results suggest that compound 6d may serve as a hit compound for further mechanistic studies.
Yazarlar (8)
1
Kaan Kucukoglu
ORCID: 0000-0001-8977-9775
2
Nagihan Faydali
ORCID: 0000-0002-8895-1825
3
Dilek Bul
4
Hayrunnisa Nadaroglu
5
Belgin Sever
ORCID: 0000-0003-4847-9711
6
Mehlika Dilek Altıntop
ORCID: 0000-0002-8159-663X
7
Bahadır Öztürk
8
Ilkay Guzel
Anahtar Kelimeler
1,2,4-Oxadiazole
Carbonic anhydrase
Cytotoxic activity
Molecular docking
Kurumlar
Anadolu Üniversitesi
Eskisehir Turkey
Atatürk Üniversitesi
Erzurum Turkey
Selçuk Üniversitesi
Selçuklu Turkey
Metrikler
3
Atıf
8
Yazar
4
Anahtar Kelime