Structural and spectral analysis of anticancer active cyclo(Ala-His) dipeptide

Area of Science:

• Computational Chemistry
• Medicinal Chemistry
• Molecular Spectroscopy

Background:

• Cyclic dipeptides exhibit significant biological activities, including anticancer properties.
• Understanding the structural and electronic properties of cyclo(Ala-His) is crucial for its therapeutic development.

Purpose of the Study:

• To determine the most stable conformation of cyclo(Ala-His) using computational methods.
• To investigate the structural and spectral properties of cyclo(Ala-His) and its dimeric forms.
• To evaluate the potential of cyclo(Ala-His) as a drug candidate through molecular docking and ADMET analysis.

Main Methods:

• Conformational analysis and Density Functional Theory (DFT) calculations.
• DFT methods (B3LYP, wb97xd) with 6-311++G(d,p) basis set for structural and spectral simulations.
• Solid-phase Fourier-transform infrared (FTIR) and Raman spectroscopy.
• In silico molecular docking with DNA.
• Drug likeness and ADMET property analysis.

Main Results:

• The boat conformation of cyclo(Ala-His) is more stable than the planar form.
• Three energetically favorable dimeric structures of cyclo(Ala-His) were identified.
• Experimental vibrational spectra (FTIR, Raman) are in good agreement with DFT-simulated spectra.
• Molecular docking suggests interaction with DNA, and ADMET analysis indicates favorable pharmacokinetic profiles.

Conclusions:

• Cyclo(Ala-His) exhibits a stable boat conformation and predictable spectral properties.
• The compound demonstrates potential for drug discovery due to favorable drug likeness and ADMET profiles.
• Further investigation into cyclo(Ala-His) as an anticancer agent is warranted.