Synthesis, Antimicrobial Activity, Molecular Docking and DFT Studies of Some New 2,5-Disubstituted Benzoxazole Derivatives

Öz

In this study, 6 original 2,5-disubstituted benzoxazole derivatives were synthesized and their structures were elucidated by 1H-NMR, 13C-NMR spectroscopy, and HRMS.Their antimicrobial activities against various Gram (+), Gram (-) bacteria, fungi, and their isolates were investigated by microdilution technique. Although antimicrobial activities of tested benzoxazole derivatives were generally weaker than reference drugs; C1, C5 and C6 derivatives showed the best activity against C. albicans isolate with MIC: 16 µg/mL. Molecular docking study of the compounds was carried out and 2D/3D protein-ligand interactions of C5 (the lowest docking score), one of the most effective compounds against C. albicans isolate, were demonstrated. In addition, HOMO-LUMO energies of all compounds and electronic parameters such as ionization potential (IP), electron affinity (EA), electronegativity (X), chemical hardness (η), chemical softness (S), chemical potential (μ) and electrophilic index (ω) obtained from these energies were calculated. The HOMO-LUMO diagram, molecular electrostatic potential analysis, and optimized molecular structures of C1, C5, and C6 were also presented visually.

Anahtar Kelimeler

• Benzoxazole
• Synthesis
• Antimicrobial activity
• DFT
• Molecular docking.

Bazı Yeni 2,5-Disübstitüe Benzoksazol Türevlerinin Sentezi, Antimikrobiyal Aktivite, Moleküler Doking ve DFT Çalışmaları

Öz

Bu çalışmada 6 adet orijinal 2,5-disübstitüe benzoksazol türevi sentezlendi ve yapıları 1H-NMR, 13C-NMR spektrokopisi ve HRMS ile aydınlatıldı. Sentezlenen bileşiklerin mikrodilüsyon tekniği ile çeşitli Gram (+), Gram (-) bakteri, mantar ve bunların izolatlarına karşı antimikrobiyal aktiviteleri incelendi. Test edilen benzoksazol türevlerinin antimikrobiyal aktiviteleri genel olarak referans ilaçlara göre daha zayıf olmakla birlikte; en iyi aktiviteyi C. albicans izolatına karşı MİK: 16 µg/mL ile C1, C5 ve C6 türevleri gösterdi. Bileşiklerin moleküler doking çalışması gerçekleştirildi ve C. albicans izotına karşı en etkili bileşiklerden biri olan C5'in (doking skoru en düşük olan) 2D/3D protein-ligand etkileşimleri gösterildi. Ayrıca tüm bileşiklerin HOMO-LUMO enerjileri ve bu enerjilerden elde edilen iyonlaşma potansiyeli (İP), elektron afinitesi (EA), elektronegatiflik (X), kimyasal sertlik (η), kimyasal yumuşaklık (S), kimyasal potansiyel (μ ) ve elektrofilik indeks (ω) gibi diğer elektronik parametreleri hesaplandı. C1, C5 ve C6’nın HOMO-LUMO diyagramı, moleküler elektrostatik potansiyel analizi ve optimize edilmiş moleküler yapıları da görsel olarak sunuldu.

Anahtar Kelimeler

• Benzoksazol
• Sentez
• Antimikrobiyal aktivite
• DFT
• Moleküler doking.

Kaynakça

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