Theoretical Investigation of 5-Fluorouracil and Tamoxifen Complex – Structural, Spectrum, DFT, ADMET and Docking Simulation

Abstract

Combination of FDA approved drugs may be more effective in biological activities by targeting different protein mechanism at a same time and less toxic. A combination of 5-Fluorouracil and tamoxifen may cause a synergistic effect and induce cancer cell death and more effective against corona virus. In this study, constructed 5-Fluorouracil with tamoxifen structure was optimized through DFT/B3LYP approach with the basis set 6-311 G. Theoretical, ultraviolet-visible spectrum was calculated, and electronic transitions were examined. The energy gap between HOMO and LUMO was used to study the combined structure’s structural stability and reactivity and the computed energy gap (ΔE) was 4.3023825 eV. The Mulliken charge distribution was assessed and the atomic charges were calculated. The molecular docking simulation was performed with breast cancer and SARS-CoV-19 target proteins. The docking scores showed that the complex compound’s binding affinity was higher, that confirms better synergistic effect of 5-Fluorouracil and tamoxifen. The complex compound’s maximum binding affinity was −8.0 Kcal/mol against caspase 6 and −8.1 Kcal/mol against furin, that showed inhibitory potential against cancer and corona virus. The pharmacokinetic properties and toxicity of the complex structure was studied, and the results showed the safety profile of the complex lead compound and can be utilized as an effective anticancer and antiviral drug.

Keywords:

• 5-Fluorouracil
• tamoxifen
• DFT
• breast cancer
• COVID-19
• ADMET

Acknowledgement

The authors acknowledge Dr. S. Athimoolam, Department of Physics, University college of Engineering, Anna University, Nagercoil for helping us in utilizing Gaussian program.

Author contribution

The work was carried out in collaboration among all authors. The complex structure was constructed by Sureba Sukumaran and Thimma Mohan Viswanathan. Structural optimization and UV-Vis spectroscopic investigation was carried out by Sureba Sukumaran and Asath Bahadur Sultan. Density function theory was performed by Sureba Sukumaran and Azar Zochedh. The anti-cancer, anti-viral activities and drug-likeness evaluation was done by Sureba Sukumaran, and Thandavarayan Kathiresan. The Validation of manuscript was done by Sureba Sukumaran and Thandavarayan Kathiresan. All authors read and approved the final manuscript.

Disclosure statement

The authors have no financial or non-financial interests to disclose.