N-(4-(4-Klorofenil)oksazol-2-il)-4-fenil-1H-pirazol-3-karboksamid Molekülünün DFT Yöntemiyle Teorik İncelenmesi ve SARS-CoV-2 Ana Proteazlarına Karşı Moleküler Doking Değerlendirilmesi

Abstract

Bu çalışmada, potansiyel biyolojik aktiviteye sahip bir benzoksazol türevi olan N-(4-(4-klorofenil)oksazol-2-il)-4-fenil-1H-pirazol-3-karboksamid (NOPC) molekülü teorik ve hesaplamalı yöntemlerle detaylı olarak incelenmiştir. Molekülün yapısal ve elektronik özellikleri, Yoğunluk Fonksiyonel Teorisi (DFT) kapsamında B3LYP ve PBEPBE metotları ile 6-31G(d,p) temel seti kullanılarak analiz edilmiştir. Bu kapsamda optimize geometri, HOMO-LUMO enerji seviyeleri, NBO analizi, Mulliken yük dağılımı, NLO özellikleri ve MEPS yüzeyi değerlendirilmiştir. Ayrıca, NOPC molekülünün SARS-CoV-2 virüsünün ana proteazları olan 6W75 ve 7BV2 ile etkileşimi moleküler doking yöntemiyle araştırılmış, sırasıyla -7,70 ve -8,40 kcal/mol bağlanma enerjileri elde edilmiştir. Bu bulgular, molekülün güçlü bağlanma afinitesi gösterdiğini ve COVID-19’a karşı potansiyel bir inhibitör olabileceğini göstermektedir. Son olarak, ADMETlab 2.0 ile yapılan ADME analizleri, NOPC’nin Lipinski kurallarına uygun olduğunu ve yüksek oral biyoyararlanım potansiyeline sahip olduğunu ortaya koymuştur. Elde edilen veriler, NOPC molekülünün ilaç tasarımı açısından umut vadeden bir aday olduğunu göstermektedir.

Keywords

• DFT
• Moleküler Doking
• ADME
• MEP
• NBO
• Benzoksazol

Theoretical Investigation of the N-(4-(4-chlorophenyl)oxazol-2-yl)-4-phenyl-1H-pyrazole-3-carboxamide Molecule by DFT Method and Molecular Docking Evaluation Against SARS-CoV-2 Main Proteases

Abstract

In this study, N-(4-(4-chlorophenyl)oxazol-2-yl)-4-phenyl-1H-pyrazole-3-carboxamide (NOPC), a benzoxazole derivative with potential biological activity, was investigated in detail by theoretical and computational methods. The structural and electronic properties of the molecule were analyzed using the 6-31G(d,p) basis set with B3LYP and PBEPBE methods within the scope of Density Functional Theory (DFT). In this context, optimized geometry, HOMO-LUMO energy levels, NBO analysis, Mulliken charge distribution, NLO properties and MEPS surface were evaluated. In addition, the interaction of the NOPC molecule with 6W75 and 7BV2, the main proteases of the SARS-CoV-2 virus, was investigated by molecular docking method, and binding energies of -7.70 and -8.40 kcal/mol were obtained, respectively. These findings indicate that the molecule exhibits strong binding affinity and may be a potential inhibitor against COVID-19. Finally, ADME analyses performed with ADMETlab 2.0 revealed that NOPC complies with Lipinski rules and has high oral bioavailability potential. The obtained data indicate that NOPC molecule is a promising candidate for drug design.

Keywords

• DFT
• Molecular Docking
• ADME
• MEP
• NBO
• Benzoxazole

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