Secoiridoids are bioactive compounds, which are present in plants and exhibit anti-inflammatory activity. In this work, to understand the structural basis of five secoiridoids; amarogentin, amaroswerin, gentiopicrin, sweroside, and swertiamarin for potent inhibitors of the target proteins associated with the collagen degradation pathway, namely MMP-1, MMP-3, MMP-9 and transcription factor AP-1, molecular docking, binding mode modeling, and MD simulations were carried out. The binding inhibitory effects of the secoiridoids were screened on these proteins. The obtained results in terms of binding conformation, binding free energy, protein–ligand interaction profile, structural flexibility, and binding energy decomposition of the secoiridoid inhibitors were elucidated. The molecular modeling clarified inhibitory effect on account of the five secoiridoids towards all three Matrix metalloproteinases (MMPs). Moreover, amarogentin and gentiopicrin may interfere with gene expression via binding to AP-1. Among all screened secoiridoids, amarogentin and gentiopicrin exhibited an interesting binding affinity to the MMPs and AP-1. The results suggest that amarogentin has the highest potential for application as an anti-aging agent with the MMP inhibitory and anti-transcriptional activities, even though further studies are needed to determine the anti-aging effect in vitro, in vivo and by clinical evaluation.
Sagar M, Pathak RK, Pandey RK, Singh DB, Pandey N, Gupta MK (2014) Binding affinity analysis and ADMET prediction of epigallocatechine gallate (EGCG) derivatives for AP-1 protein: a drug target for liver cancer. Netw Model Anal Health Inform Bioinform 3:66. https://doi.org/10.1007/s13721-014-0066-xCrossRefGoogle Scholar
Singh T, Adekoya OA, Jayaram B (2015) Understanding the binding of inhibitors of matrix metalloproteinases by molecular docking, quantum mechanical calculations, molecular dynamics simulations, and a MMGBSA/MMBappl study. Mol Biosyst 11:1041–1051. https://doi.org/10.1039/C5MB00003CCrossRefPubMedGoogle Scholar
Suryawanshi S, Mehrotra N, Asthana RK, Gupta RC (2006) Liquid chromatography/tandem mass spectrometric study and analysis of xanthone and secoiridoid glycoside composition of Swertia chirata, a potent antidiabetic. Rapid Commun Mass Spectrom 20:3761–3768. https://doi.org/10.1002/rcm.2795CrossRefPubMedGoogle Scholar
Wongrattanakamon P, Nimmanpipug P, Sirithunyalug B, Jiranusornkul S (2017) Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules. Mol Cell Biochem. https://doi.org/10.1007/s11010-017-3196-5PubMedGoogle Scholar
Zhang W, Laursen RA (1998) Structure-function relationships in a type I antifreeze polypeptide. The role of threonine methyl and hydroxyl groups in antifreeze activity. J Biol Chem 273:34806–34812CrossRefPubMedGoogle Scholar