Exploring the Synergistic Effect of Tegafur-Syringic Acid Adduct Against Breast Cancer through DFT Computation, Spectroscopy, Pharmacokinetics and Molecular Docking Simulation

Abstract

The most prevalent kind of cancer and the main reason for cancer-related deaths in women is breast cancer. Synergistic drug delivery plays an effective role in the treatment of cancer by targeting various proteins underlying different mechanism. In this present study, a thorough analysis of the tegafur syringic acid adduct compound using density functional theory, molecular docking and pharmacokinetic prediction has been done. The PED value was given to the estimated vibrational wavenumbers. The molecule’s UV-Vis absorption spectra in the gas phase and liquid phase (water), were exhibited as π→π* electronic transitions. In order to determine the stability and molecular reactivity of the molecule, the HOMO-LUMO energies, energy gap, molecular electrostatic potential surface and mulliken atomic charge distribution were determined. Natural bond orbital analysis was used to determine the molecule’s second order perturbation energy E(2) values and potential reactive location was revealed through local reactivity descriptors. The Hirshfeld surface analysis showed that H…H (40.9%), O…H/H…O (27.2%), C…C (8%), O…C/C…O (7.8%), F…H/H…F (5.9%), C…H/H…C (5.5%), and N…C/C…N (2.9%) have the highest percentage contributions of the most important interactions. Thermodynamic characteristics like enthalpy, specific heat capacity and entropy were calculated. The physiochemical, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties were predicted and represented the safety profile of adduct compound and the docking studies exhibited the binding potential of the adduct against the breast cancer proteins and highest binding affinity was observed against GSK3β with docking score of −9.7 Kcal/mol.

Keywords:

• Tegafur
• syringic acid
• DFT
• ADMET
• molecular docking

Author contributions

The work was carried out in collaboration among all authors. Conceptualization was by A.B.S. Quantum chemical calculation was performed by A.Z., A.S. and A.B.S. The Hirshfeld surface analysis was done by A.B.S. and A.S. The molecular docking analysis was performed by K.C. and A.Z. Pharmacokinetic prediction were done by A.Z. The writeup of the manuscript was done by A.Z., K.C. and A.B.S. The validation of manuscript was done by A.S. and A.B.S. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).