Synthesis of 1-Piperoylpiperidine Investigated Through Spectroscopy, Quantum Computation, Pharmaceutical Activity, Docking and MD Simulation Against Breast Cancer

Abstract

1-Piperoylpiperidine (1-PIP) was crystallized as a single unit by a slow evaporation process, and it was examined using XRD and FT-IR spectroscopy. The centrosymmetric monoclinic structure is confirmed by XRD. The functional groups were determined by experimental FT-IR range from 4000 to 400 cm⁻¹. Density functional theory was used to do calculations on quantum chemistry on B3LYP/6-311++G (d,p) theory. The vibrational wavenumbers were calculated, and experimentally obtained were assigned and compared. The molecule’s reactivity and kinetic stability are revealed via molecular orbital research. The Mulliken atomic charge distribution and molecular electrostatic potential analyses provide additional evidence of the molecule’s reactive site. The electronic spectrum was computed through TD-DFT and the electronic transition was attained at π→π*. The molecule’s bioactivity is shown by the natural bond orbital analysis. The efficiency and contribution of interactions between various atoms were evaluated using the Hirshfeld analysis. The DPPH assay was performed to access the antioxidant ability of 1-PIP. The disk diffusion test exhibited the antibacterial efficiency of 1-PIP molecule. The safety profile of 1-PIP was confirmed through physiochemical and pharmacokinetic predictions. In silico docking evaluation was performed for 1-PIP against 10 breast cancer-aided proteins and the higher binding affinity was recorded for NAMPT, which was further investigated through molecular dynamic (MD) simulation. MD simulation for a time period of 50 ns confirmed the stability of 1-PIP bounded NAMPT structure.

Keywords:

• 1-Piperoylpiperidine
• breast cancer
• DFT
• ADMET
• molecular dynamic simulation

Acknowledgments

The authors acknowledge Dr. S. Athimoolam, Department of Physics, University college of Engineering, Nagercoil for helping us in utilizing Gaussian 09 Program.

Author contributions

The work was carried out in collaboration among all authors. Conceptualization by T.K and A.B.S. Crystallization and characterization was done by K.C and T.K. Quantum chemical investigation was performed by K.C and A.Z. The anti-bacterial, antioxidant, anti-cancer activities and drug-likeness evaluation were done by K.C., A.Z and T.K. The write-up was carried out by K.C, A.Z. A.B.S. and T.K. Validation of manuscript was done by T. K. and A.B.S. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a Grant-aid from the Department of Biotechnology (DBT) (BT/PR44695/NER/95/1880/2021).