Computational Approaches to Deciphering Binding Interactions among Tyrosinase and Urokinase-type Plasminogen Activator with Methimazole and Tranexamic Acid as Two Off-Label Antimelasmic Drugs
Arezou Lari1, Saeed Ivani2, Maryam Haghkhah1, Sara Ivani3
Affiliation
- 1Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Islamic Republic of Iran
- 2Department of Biomedical Engineering and Medical Physics, ShahidBeheshti University of Medical Science, Tehran, Islamic Republic of Iran
- 3Department of Mathematics, Faculty of Science, Razi University, Kermanshah, Islamic Republic of Iran
- 4Department of Biology, Faculty of Science, Razi University, Kermanshah, Islamic Republic of Iran
Corresponding Author
Isaac Karimi; Department of Biology, Faculty of Science, Razi University, Kermanshah, Islamic Republic of Iran. E-mail: isaac_karimi2000@yahoo.com, karimiisaac@razi.ac.ir
Citation
Isaac Karimi., et al. Computational Approaches to Deciphering Binding Interactions among Tyrosinase and Urokinase- Type Plasminogen Activator with Methimazole and Tranexamic Acid as Two Off label Antimelasmic Drugs (2017) Bioinfo Proteom Img Anal 3(1):182- 186
Copy rights
© 2017 Isaac Karimi. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Keywords
Abstract
Tyrosinase is rate-limiting enzyme for melanogenesis and urokinase-type plasminogen activator (uPA) plays an autocrine role in growth, differentiation and migration of keratinocyte involving in melanogenesis. Molecular dynamics simulations were performed to investigate the interaction of uPA and tyrosinase with methimazole (MIM) and tranexamic acid (TA) as two off-label antimelasmic drugs. Our findings showed that TA has more negative binding affinity to tyrosinase (-14.58 Kcal/mol) than that of uPA (-5.9 Kcal/mol) therefore its antimelasmic activity may be mediated through inhibition of tyrosinase with inhibition constant (IC) 20.5 pM rather than inhibition of uPA with IC 47.67 uM. Methimazole has approximately equal binding affinity to tyrosinase (-4.25 Kcal/mol) and uPA (-3.77 Kcal/mol) with IC 765.79 uM and 1.73 mM respectively. However MIM docked more stable with uPA. It seems that uPA plays more important role in antimelasmic activity of MIM. In conclusion, this in silico investigation prepared a theoretical framework that determines beneficial therapeutic effects of TA and MIM in hypermelanistic conditions like melasma.
