Scopus
YÖKSİS Eşleşti
Synthesis, molecular modeling, quantum mechanical calculations and ADME estimation studies of benzimidazole-oxadiazole derivatives as potent antifungal agents
Journal of Molecular Structure · Mart 2022
YÖKSİS Kayıtları
Synthesis, molecular modeling, quantum mechanical calculations and ADME estimation studies of benzimidazole-oxadiazole derivatives as potent antifungal agents
Journal of Molecular Structure · 2022 SCI-Expanded
DOKTOR ÖĞRETİM ÜYESİ AYŞEN IŞIK →
Makale Bilgileri
DergiJournal of Molecular Structure
Yayın TarihiMart 2022
Cilt / Sayfa1252
Scopus ID2-s2.0-85121122790
Özet
In this study, a series of new 3-((5-(4-(5-substitue-1H-benz[d]imidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio)-1-phenyl propane-1-on (4a-4d) derivatives has been designed and synthesized as probable antifungal agents. The final compounds were screened for antifungal activity against Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019) and Candida albicans (ATCC 24433) by employing the broth micro-dilution method. All the new compounds’ structures were elucidated by 1H NMR, 13C NMR, and MS spectral data analysis results. The results demonstrated that compounds 4a (MIC50=0,78 µg/mL) and 4b (MIC50=0,78 µg/mL) possessed better inhibitory activity against C. albicans than ketoconazole (MIC50=1,56 µg/mL). Molecular docking studies of compounds were performed at the active site of 14-alpha demethylase and estimated ADME profiles were calculated. Furthermore, 100 ns simulations were carried out of CYP51-4a, CYP51-4b, CYP51-4c, & CYP51-4d, protein-ligand complexes which revealed mean RMSD values are 0.22, 0.28, 0.26, and 0.23 nm, respectively. The simulation result shows lead compounds bound tightly within the cavity of the CYP51 target protein and thus having conformational stability. The simulation and MM/PBSA results reveal that all ligand-protein complexes are stable and have stable interactions till 100 ns simulation time. Thus, these synthesized lead compounds can be further analyzed for in vitro, in vivo experimental validation as antifungal candidates.
Yazarlar (8)
1
Ulviye Acar Çevik
ORCID: 0000-0003-3537-2544
2
Ismail Celik
ORCID: 0000-0002-8146-1663
3
Ayşen Işık
4
Renjith Raveendran Pillai
5
Trina Ekawati Tallei
6
Rohitash Yadav
7
Yusuf Özkay
8
Zafer Asım Kaplancıklı
Anahtar Kelimeler
Benzimidazole
DFT
Molecular docking
Molecular dynamics
Kurumlar
All India Institute of Medical Sciences, Rishikesh
Rishikesh India
Anadolu Üniversitesi
Eskisehir Turkey
Erciyes Üniversitesi
Kayseri Turkey
Selçuk Üniversitesi
Selçuklu Turkey
Universitas Sam Ratulangi
Manado Indonesia
University College, Thiruvananthapuram
Thiruvananthapuram India
Metrikler
30
Atıf
8
Yazar
4
Anahtar Kelime