Potentially Bioactive Novel Isophthalic Acid Based Azo Molecules: Synthesis, Characterization, Quantum Chemical Calculations, ADMET Properties, Molecular Docking and Molecular Dynamics Simulations

Abstract

We report here the synthesis of the two novel molecules 5-((5-hexyl-2,4-dihydroxyphenyl)diazenyl)isophthalic acid (3a) and 5-((5-ethyl-2,4-dihydroxyphenyl)diazenyl)isophthalic acid (3b). The structures of the 3a and 3b were confirmed by using ¹H-NMR,¹³C-NMR, FT-IR, UV-vis, and HR-ESI-MS techniques. The optimized molecular geometry, vibrational frequency,¹H- and ¹³C-NMR spectra calculations were performed using the DFT/B3LYP method with a 6-311G(d,p) basis set. The frontier molecular orbitals and electronic transition wavelengths were calculated at the level of TD-DFT/CAM-B3LYP/6-311G(d,p). The experimental data obtained for the synthesized molecules were in good agreement with the theoretical ones. The calculated HOMO-LUMO band gap revealed that 3a has a softer character and may be more reactive in chemical reactions. Important ADMET parameters of the compounds were also calculated, and the obtained physicochemical, pharmacokinetic, drug similarity, and toxicity data were at the desired level for a candidate bioactive compound. In order to examine the potential anticancer or antibacterial properties of newly synthesized azo molecules, molecular docking studies were performed using four different proteins. The best interaction was determined to be between 3a and VEGFR2 (PDB ID: 2XIR) with a binding energy of 9.0 kcal/mol. Moreover, a 50 ns MD simulation study for 3a-2XIR revealed that the complex maintained both its structural integrity and molecular interactions throughout the simulation.

Graphical Abstract

Keywords:

• Azo molecules
• density functional theory
• anticancer
• molecular docking
• molecular dynamics simulation

Competing interests

There is no competing interest.

Ethical approval

Not applicable.

Authors’ contributions

Conceptualization: Mehmet ULUTÜRK, Tahir TİLKİ

Software: Bülent DEDE, Çiğdem KARABACAK ATAY

Investigation: Mehmet ULUTÜRK, Çiğdem KARABACAK ATAY, Bülent DEDE

Visualization: Bülent DEDE, Çiğdem KARABACAK ATAY

Writing – Original Draft: Mehmet ULUTÜRK, Çiğdem KARABACAK ATAY, Bülent DEDE

Writing – Review & Editing: Mehmet ULUTÜRK, Çiğdem KARABACAK ATAY, Bülent DEDE, Tahir TİLKİ

Supervision: Tahir TİLKİ

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

No data availability.

Additional information

Funding

Not applicable.