Antibacterial Potential of Trihydroxycyclohexa-2,4-Diene-1-Carboxylic Acid: Insight from DFT, Molecular Docking, and Molecular Dynamic Simulation

In this study, (z)-5-((3-(2,3-dihydroxyphenyl) acryloyl) oxy)- 1,3,4-trihydroxycyclohexa-2,4-diene-1-carboxylic acid (chlorogenic acid) was isolated and characterized using UV-Visible, H-1 NMR and C-13 NMR, FT-IR, along with detailed investigation using density functional theory (DFT), in-silico molecular docking, and molecular dynamics (MD) simulation. Results from DFT calculation indicates that the titled compound is very stable with energy gap of 3.7-7.8 for variable functionals, and similarly, the structural parameters show very close agreement with X-ray data for bond lengths and angles. The FT-IR spectrum results revealed stretching vibration O-H (3366 cm(-1)), C=O (1689 cm(-1)), C-H (1636, 1606, 1522, and 1442 cm(-1)), C-O (1192 and 1122 cm(-1)). The drug-likeness analyses and ADME studies showed drug-likeness ability and good oral behavior of the investigated compound as it obeys Lipinski, Ghose, Veber and Egan rules. Hepatotoxic and immunotoxic activities were indicated for the toxicity/toxicological endpoints of the studied compound. The molecular docking indicates a binding affinity of -8.30 and 9.5 kcal/mol for the titled compound, which is higher than the standard drug. From the molecular dynamic simulation results, chlorogenic-2H14 (complex B) revealed variations in RMSD values of less than 3 angstrom, indicating that the protein structure underwent minor conformational changes throughout the simulation. Chlorogenic-protein complexes had average RGyr values of 3.704 - 4.907 angstrom, which indicates compaction during the simulation. Therefore, it can be said that the titled compound has potential to be effective as an agent for cholera management, and the results obtained can be platform further in-vitro, vivo and clinical trials.

Automated summary

In this study, chlorogenic acid was successfully isolated and characterized using various techniques. The compound showed good stability, drug-like properties and oral behavior. Molecular docking results indicated a high binding affinity of chlorogenic acid with proteins. Molecular dynamics simulation showed minor conformational changes in the protein structure. Therefore, chlorogenic acid has the potential to be an effective agent for cholera management.