Next Article in Journal
Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress
Previous Article in Journal
Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma
Open AccessArticle

Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1

by 1,†, 1,†, 2 and 1,3,*
1
Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Korea
2
Department of Physics, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, Uttar Pradesh 273009, India
3
Stemforce, 313 Institute of Industrial Technology, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(10), 1379; https://doi.org/10.3390/biom10101379
Received: 27 August 2020 / Revised: 17 September 2020 / Accepted: 24 September 2020 / Published: 28 September 2020
(This article belongs to the Section Biomacromolecules)
Matrix metalloproteinases 1 (MMP-1) energetically triggers the enzymatic proteolysis of extracellular matrix collagenase (ECM), resulting in progressive skin aging. Natural flavonoids are well known for their antioxidant properties and have been evaluated for inhibition of matrix metalloproteins in human. Recently, (-)-epicatechin and proanthocyanidin B2 were reported as essential flavanols from various natural reservoirs as potential anti-inflammatory and free radical scavengers. However, their molecular interactions and inhibitory potential against MMP-1 are not yet well studied. In this study, sequential absorption, distribution, metabolism, and excretion (ADME) profiling, quantum mechanics calculations, and molecular docking simulations by extra precision Glide protocol predicted the drug-likeness of (-)-epicatechin (−7.862 kcal/mol) and proanthocyanidin B2 (−8.145 kcal/mol) with the least reactivity and substantial binding affinity in the catalytic pocket of human MMP-1 by comparison to reference bioactive compound epigallocatechin gallate (−6.488 kcal/mol). These flavanols in docked complexes with MMP-1 were further studied by 500 ns molecular dynamics simulations that revealed substantial stability and intermolecular interactions, viz. hydrogen and ionic interactions, with essential residues, i.e., His218, Glu219, His222, and His228, in the active pocket of MMP-1. In addition, binding free energy calculations using the Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method suggested the significant role of Coulomb interactions and van der Waals forces in the stability of respective docked MMP-1-flavonol complexes by comparison to MMP-1-epigallocatechin gallate; these observations were further supported by MMP-1 inhibition assay using zymography. Altogether with computational and MMP-1–zymography results, our findings support (-)-epicatechin as a comparatively strong inhibitor of human MMP-1 with considerable drug-likeness against proanthocyanidin B2 in reference to epigallocatechin gallate. View Full-Text
Keywords: matrix metalloproteinases 1; epicatechin; proanthocyanidin B2; molecular dynamics simulation; zymography matrix metalloproteinases 1; epicatechin; proanthocyanidin B2; molecular dynamics simulation; zymography
Show Figures

Figure 1

MDPI and ACS Style

Lee, K.E.; Bharadwaj, S.; Yadava, U.; Kang, S.G. Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1. Biomolecules 2020, 10, 1379. https://doi.org/10.3390/biom10101379

AMA Style

Lee KE, Bharadwaj S, Yadava U, Kang SG. Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1. Biomolecules. 2020; 10(10):1379. https://doi.org/10.3390/biom10101379

Chicago/Turabian Style

Lee, Kyung E.; Bharadwaj, Shiv; Yadava, Umesh; Kang, Sang G. 2020. "Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1" Biomolecules 10, no. 10: 1379. https://doi.org/10.3390/biom10101379

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop