MOLECULAR DOCKING ANALYSIS OF CHLOROGENIC ACID AND 3,5-DI-O-CAFFEOYLQUINIC ACID REVEALS STRONG INHIBITORY INTERACTIONS WITH COX-2 AND MAPK SIGNALING PROTEINS

Abstract

 Inflammation is a key factor in many chronic diseases, and natural polyphenols are emerging as good regulators of inflammatory signaling. An in silico molecular docking analysis was done to assess the potential inhibitory effects of chlorogenic acid and 3,5-di-O-caffeoylquinic acid at two relevant pro-inflammatory targets Cyclooxygenase-2 (COX-2) and Mitogen-activated Protein Kinases (MAPKs). The docking resulted demonstrated both ligands were able to form stable and favorable energy-complex binding to the active sites of COX-2 and MAPKs. Chlorogenic acid was found to have a −7.4 kcal/mol binding energy to MAPKs and formed hydrogen bonding and hydrophobic interactions with ALA93, ARG5, PHE348, and ASP88. For 3,5-di-O-caffeoylquinic acid, a larger −9.95 kcal/mol binding energy was calculated and multiple stabilizing interactions at TYR311, TYR132, ARG136, ASN82, and the remaining residues of the catalytic-region were observed.Concerning COX-2, chlorogenic acid engaged through hydrogen bonds with CYS36, HIS39, ASN43, and ARG44, and 3,5-di-O-caffeoylquinic acid exhibited remarkably favorable predicted ΔGtab and Ki value of −10.9 kcal/mol and kang of around 10 nM, respectively, primarily due to strong hydrogen bonding interactions and π–π interactions with the COX-2 binding pocket. Similar to chlorogenic acid, we conclude that both polyphenols possess robust dual-target inhibitory potential worth considering, especially in the case of 3,5-di-O-caffeoylquinic acid, which may be a potent modulator of inflammation through inhibiting COX-2 and MAPK-mediated signaling. The findings provide important rationales in developing further experimental studies and elucidate the clinical translation of natural compound-therapeutics for anti-inflammatory pathways.