Combinatorial Effect of Syringic Acid-Pyrazinamide Adduct against Luminal Type Breast Cancer Investigated through DFT, Drug-Likeness, and Molecular Docking Simulation

Abstract

Luminal type breast cancer is a type of breast cancer that has a favorable prognosis in comparison to other forms. In accordance with the proliferation index, luminal-type breast malignancy is divided as luminal A and B types. The combination of two molecules will be a more effective strategy for the treatment of breast cancer. In this study, the structural and different spectroscopic parameters for the 4-hydroxy3, 5-dimethoxybenzoic acid-pyrazine 2-carboxamide cocrystal were calculated using quantum mechanics employing the B3LYP/6–311++G (d,p) approach. With the use of XRD data, the optimized geometrical parameters were compared. The HOMO-LUMO, molecule electrostatic potential surfaces, and vibrational investigations of the cocrystal are all computed. The possibility of charge transmission inside the particle is demonstrated by the minimal HOMO–LUMO energy gap. The existence of intermolecular OH…O hydrogen bonds, which are brought about by the interface of the oxygen lone pair with the anti-bonding orbital, was demonstrated by NBO examination. The drug-likeness possessions exhibited the safety profile of the 4-hydroxy-3,5-dimethoxybenzoic acid-pyrazine-2-carboxamide adduct. The results of molecular docking indicate that the cocrystal of 4-hydroxy3, 5-dimethoxybenzoic acid and pyrazine 2-carboxamide revealed better binding ability against luminal type breast cancer proteins with docking values of −8.3, −7.6, and −8.7 kcal/mol.

Keywords:

• Co-crystal
• DFT
• Hirshfeld analysis
• Molecular Docking
• ADMET

Author contribution

The work was carried out in collaboration among all authors. Conceptualization was by A.B.S and A.Z. Quantum chemical calculation was performed by M.P., A.Z., and A.B.S. The hirshfeld surface analysis was done by P.K., A.B.S., and A.S. The molecular docking and pharmacokinetic prediction were done by M.P and A.Z. The write up of the manuscript was done by M.P, A.Z., and A.B.S. The validation of manuscript was done by A.Z., 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).