DFT, In Vitro Antimicrobial, HCV, HBV, HAV, and Breast Cancer Molecular Docking Exploration of 6-[(E)-(4-Hydroxy-2,5-dinitrophenyl)diazenyl]-2H-chromen-2-one and 6-[(E)-(10-Hydroxy-9-anthryl)diazenyl]-2H-chromen-2-one

• Published in: Russian journal of bioorganic chemistry Vol. 50; no. 3; pp. 1049 - 1066
• Main Authors: Abdou, Aly, Mostafa, H. M., Abdel-Mawgoud, Abdel-Mawgoud M.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2024; Springer Nature B.V
• Subjects: Antimicrobial agents; Bacteria; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Breast cancer; Chemical activity; Chemical potential; Density functional theory; Electronegativity; Energy gap; Fungi; Hepatitis A; Hepatitis B; Hepatitis C; Life Sciences; Molecular docking; Optimization; Organic Chemistry; Reactivity; Receptors; Softness; Viruses; antimicrobial; DFT; molecular docking; azo-coumarine
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162024030294

Objective: The objective of this study was to investigate the 3D geometry optimization, theoretical spectroscopic features, chemical reactivity, antimicrobial activity, and inhibitory potential of two azo-coumarine derivatives, namely 6-[( E )-(4-hydroxy-2,5-dinitrophenyl)diazenyl]-2 H -chromen-2-one ( L1 ) and 6-[( E )-(10hydroxy-9-anthryl)diazenyl]-2 H -chromen-2-one ( L2 ). Methods: The 3D geometry optimization of the compounds was conducted using density functional theory (DFT) at the B3LYP/6-311G (d,p) level of theory. Theoretical infrared (IR) and UV-Vis spectral features were computed and compared with experimental values to validate the theoretical approach. Chemical reactivity was assessed based on electronic chemical descriptors such as energy gap (ΔE), electronegativity (χ), electronic chemical potential (μ), global chemical hardness (η), global softness (σ), global electrophilicity index (ω), and nucleophilicity index (Nu). The antimicrobial activity of the compounds was evaluated against pathogenic bacteria and fungi using the disc diffusion method. Molecular docking studies were performed to investigate the inhibitory potential of the compounds against receptors associated with breast cancer (PDB ID: 3I89), hepatitis C virus (HCV; PDB ID: 5TRH), hepatitis B virus (HBV; PDB ID: 5T2P), and hepatitis A virus (HAV; PDB ID: 5WTG). Results and Discussion: The study revealed good agreement between the experimental and theoretical spectroscopic data, indicating the reliability of the computational approach. The electronic chemical descriptors suggested the chemical reactivity and stability of the compounds, with lower energy gap (ΔE) values indicating higher reactivity. The antimicrobial screening showed promising results, with the compounds exhibiting significant antimicrobial activity against both Gram-positive and Gram-negative bacteria as well as fungi, as evidenced by their lower MIC values. Molecular docking simulations suggested that the studied compounds have the potential to act as inhibitors against the receptors associated with breast cancer and various hepatitis viruses, highlighting their possible utility in antiviral and anticancer treatment strategies. Conclusions: In conclusion, the azo-coumarine derivatives ( L1 ) and ( L2 ) demonstrated favorable theoretical and experimental characteristics, including structural optimization, spectroscopic features, chemical reactivity, antimicrobial activity, and inhibitory potential against viral receptors. These findings suggest that ( L1 ) and ( L2 ) hold promise as potential candidates for further development as antimicrobial and antiviral agents, as well as for their potential application in cancer therapeutics.