Quantum-chemical investigation on 5-fluorouracil anticancer drug

• Published in: Structural chemistry Vol. 28; no. 4; pp. 1093 - 1109
• Main Authors: Mohamed, Hala Sh, Dahy, AbdelRahman A., Hassan, Galal S., Eid, Samir-Shehata M., Mahfouz, Refaat M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer Nature B.V
• Subjects: Affinity; Cancer; Chemical bonds; Chemical reactions; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Deoxyribonucleic acid; DNA; Electron density; Exchanging; Hydrogen bonding; Mapping; Molecular docking; Molecular structure; Original Research; Physical Chemistry; Quantum chemistry; Serum albumin; Stabilization; Theoretical and Computational Chemistry; Uracil; 5-fluorouracil (5-FU); Spectroscopic investigation; Photon-irradiation; DFT calculations; Biological activity; Molecular docking
• ISSN: 1040-0400; 1572-9001
• DOI: 10.1007/s11224-017-0913-3

DFT with B3LYP/6-311++G(d,p) level were used for all calculations in this work. In biological system, 5-FU-3H 2 O has the highest stabilization energy compared to 5-FU-3NH 3 , 5-FU dimer, and 5-FU monomer. The chemical interactions of 2′-deoxyribose radical with uracil and 5-FU radicals to form 2′-deoxyuridine and 2′-deoxy-5-fluorouridine show that the difference in stabilization energies, ΔE, for their formation are quite low which facilitates the exchange reactions in DNA structure. Size, shape density distributions, and chemical reactivity sites of 5-FU were obtained by mapping electron density isosurface with electronic surface. Additionally, the intermolecular hydrogen bonding in 5-FU (sugar-phosphate) backbone system was simulated by NBO analysis to describe the role of intermolecular hydrogen bonding on the structure and chemical reactivity of 5-FU in biological systems. Molecular docking study of the interaction between 5-FU and human serum albumin (HSA) indicated that 5-FU binds to HSA with low affinity and low specificity compared to other anticancer drugs.