Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Binding Mode Prediction and Identification of New Lead Compounds from Natural Products as 3-OST Enzyme Inhibitors

Author(s): Rui Sousa, Narayana Subbiah Hari Narayana Moorthy*, Pedro Alexandrino Fernandes, Maria Joao Ramos and Natércia Fernandes Brás

Volume 17, Issue 9, 2020

Page: [1186 - 1196] Pages: 11

DOI: 10.2174/1570180817666200313105944

Price: $65

Abstract

Background and Introduction: The availability of antiviral medicines for the treatment of viral diseases is limited, hence the discovery of novel bioactive molecules is required. The present investigation has been carried out to develop novel 3-O-sulfotransferase enzyme inhibitors to treat viral diseases.

Methods: Virtual screening study (QSAR, docking and pharmacophore analysis) and binding mode analysis have been performed on a dataset collected from the literature (synthetic and natural compounds).

Results and Discussion: The docking studies showed that Glu184, His186, Lys215 and Lys368 residues established the most important hydrogen bonding with several hit compounds. The QSAR results explained that the presence of electronegative atoms/groups in the aromatic or heteroaromatic rings confer increased activity. Furthermore, the flexibility and the aromatic rings with less polar groups have better activity than the compounds connected to purine rings. Finally, the structurebased pharmacophore studies illustrated that the ligand has many polar interaction sites, and the projected acceptor and donor groups in the molecules make a significant contribution to the pharmacophore model building.

Conclusion: These studies identified two compounds, Phomoidride B and Barceloneic acid A, as potential 3-OST inhibitors.

Keywords: 3-OST, HSV-1 infections, virtual screening, heparan sulfate, QSAR, pharmacophore.

« Previous
Graphical Abstract

[1]
Rabenstein, D.L. Heparin and heparan sulfate: Structure and function. Nat. Prod. Rep., 2002, 19(3), 312-331.
[http://dx.doi.org/10.1039/b100916h] [PMID: 12137280]
[2]
O’Donnell, C.D.; Tiwari, V.; Oh, M.J.; Shukla, D. A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread. Virology, 2006, 346(2), 452-459.
[http://dx.doi.org/10.1016/j.virol.2005.11.003] [PMID: 16336986]
[3]
Tiwari, V.; O’Donnell, C.D.; Oh, M.J.; Valyi-Nagy, T.; Shukla, D. A role for 3-O-sulfotransferase isoform-4 in assisting HSV-1 entry and spread. Biochem. Biophys. Res. Commun., 2005, 338(2), 930-937.
[http://dx.doi.org/10.1016/j.bbrc.2005.10.056] [PMID: 16259945]
[4]
Xu, D.; Tiwari, V.; Xia, G.; Clement, C.; Shukla, D.; Liu, J. Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and its role in assisting the entry of herpes simplex virus type 1. Biochem. J., 2005, 385(Pt 2), 451-459.
[http://dx.doi.org/10.1042/BJ20040908] [PMID: 15303968]
[5]
Edavettal, S.C.; Lee, K.A.; Negishi, M.; Linhardt, R.J.; Liu, J.; Pedersen, L.C. Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1. J. Biol. Chem., 2004, 279(24), 25789-25797.
[http://dx.doi.org/10.1074/jbc.M401089200] [PMID: 15060080]
[6]
Moon, A.F.; Edavettal, S.C.; Krahn, J.M.; Munoz, E.M.; Negishi, M.; Linhardt, R.J.; Liu, J.; Pedersen, L.C. Structural analysis of the sulfotransferase (3-o-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1. J. Biol. Chem., 2004, 279(43), 45185-45193.
[http://dx.doi.org/10.1074/jbc.M405013200] [PMID: 15304505]
[7]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[8]
Sousa, R.P.; Fernandes, P.A.; Ramos, M.J.; Brás, N.F. Insights into the reaction mechanism of 3-O-sulfotransferase through QM/MM calculations. Phys. Chem. Chem. Phys., 2016, 18(16), 11488-11496.
[http://dx.doi.org/10.1039/C5CP06224A] [PMID: 27063019]
[9]
Dennington, R.; Keith, T.; Millam, J. GaussView, Version 5. Semichem Inc; Semichem Inc.: Shawnee Mission, KS, 2009.
[10]
Cerqueira, N.M.F.S.A.; Ribeiro, J.; Fernandes, P.A.; Ramos, M.J. vsLab-An implementation for virtual high-throughput screening using AutoDock and VMD. Int. J. Quantum Chem., 2011, 111(6), 1208-1212.
[http://dx.doi.org/10.1002/qua.22738]
[11]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[12]
Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph., 1996, 14(1), 33-38-27-28.
[http://dx.doi.org/10.1016/0263-7855(96)00018-5] [PMID: 8744570]
[13]
Schrodinger, LLC The PyMOL Molecular Graphics System Version 1.8, . 2015.
[14]
Chapman, E.; Ding, S.; Schultz, P.G.; Wong, C.H. A potent and highly selective sulfotransferase inhibitor. J. Am. Chem. Soc., 2002, 124(49), 14524-14525.
[http://dx.doi.org/10.1021/ja021086u] [PMID: 12465948]
[15]
Best, M.D.; Brik, A.; Chapman, E.; Lee, L.V.; Cheng, W.C.; Wong, C.H. Rapid discovery of potent sulfotransferase inhibitors by diversity-oriented reaction in microplates followed by in situ screening. ChemBioChem, 2004, 5(6), 811-819.
[http://dx.doi.org/10.1002/cbic.200300841] [PMID: 15174164]
[16]
Abraham, D.J. Burger’s Medicinal Chemistry and Drug Discovery; Wiley & Sons: New York, 2003, Vol. 1, .
[http://dx.doi.org/10.1002/0471266949]
[17]
Butler, M.S. Natural products to drugs: Natural product derived compounds in clinical trials. Nat. Prod. Rep., 2005, 22(2), 162-195.
[http://dx.doi.org/10.1039/b402985m] [PMID: 15806196]
[18]
Newman, D.J.; Cragg, G.M.; Snader, K.M. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod., 2003, 66(7), 1022-1037.
[http://dx.doi.org/10.1021/np030096l] [PMID: 12880330]
[19]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olsan, A.J. Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19, 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[20]
Molecular Operating Environment (MOE)Mol Oper Environ (MOE) ; Chemical Computing Group Inc.: 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, , 2016.
[21]
Lin, A. QuaSAR Descriptors., Available at:. https://www.chemcomp.com/journal/descr.htm [Accessed: February 13, 2017].
[22]
StatSoft Inc. StatSoft. Statistica data analysis software system, version 8. , http://www.statsoft.com/2013
[23]
Moorthy, N.S.H.N.; Ramos, M.J.; Fernandes, P.A. hERG binding feature analysis of structurally diverse compounds by QSAR and fragmental analysis. RSC Advances, 2011, 1, 1126-1136.
[http://dx.doi.org/10.1039/c1ra00131k]
[24]
Moorthy, N.S.H.N.; Ramos, M.J.; Fernandes, P.A. Structural analysis of α-glucosidase inhibitors by validated QSAR models using topological and hydrophobicity based descriptors. Chemom. Intell. Lab. Syst., 2011, 109, 101-112.
[http://dx.doi.org/10.1016/j.chemolab.2011.02.010]
[25]
Rabbani, G.; Baig, M.H.; Jan, A.T.; Ju Lee, E. Khan, M.V.; Zaman, M.; Farouk, A.E.; Khan, R.H.; Choi, I.. Binding of erucic acid with human serum albumin using a spectroscopic and molecular docking study. Int. J. Biol. Macromol., 2017, 105(Pt 3), 1572-1580.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.04.051] [PMID: 28414112]
[26]
Chen, C.; Layton, M.E.; Sheehan, S.M.; Shair, M.D. Synthesis of (+)-CP-263,114. J. Am. Chem. Soc., 2000, 122, 7424-7425.
[http://dx.doi.org/10.1021/ja001958x]
[27]
Dabrah, T.T.; Kaneko, T.; Massefski, W.J.; Whipple, E.B. CP-225, 917 and CP-263,114: Novel RAS farnesylation inhibitors from an unidentified fungus. 2. Structure elucidation. J. Am. Chem. Soc., 1997, 119, 1594-1598.
[http://dx.doi.org/10.1021/ja961000v]
[28]
Jayasuriya, H.; Ball, R.G.; Zink, D.L.; Smith, J.L.; Goetz, M.A.; Jenkins, R.G.; Nallin-Omstead, M.; Silverman, K.C.; Bills, G.F.; Lingham, R.B.; Singh, S.B.; Pelaez, F.; Cascales, C. Barceloneic acid A, a new farnesyl-protein transferase inhibitor from a Phoma species. J. Nat. Prod., 1995, 58(7), 986-991.
[http://dx.doi.org/10.1021/np50121a002] [PMID: 7561907]
[29]
Moorthy, N.S.H.N.; Cerqueira, N.S.; Ramos, M.J.; Fernandes, P.A. QSAR analysis of 2-benzoxazolyl hydrazone derivatives for anticancer activity and its possible target prediction. Med. Chem. Res., 2012, 21, 133-144.
[http://dx.doi.org/10.1007/s00044-010-9510-3]
[30]
Moorthy, N.S.H.N.; Ramos, M.J.; Fernandes, P.A. Analysis of van der Waals surface area properties for human ether-a-go-go-related gene blocking activity: Computational study on structurally diverse compounds. SAR QSAR Environ. Res., 2012, 23(5-6), 521-536.
[http://dx.doi.org/10.1080/1062936X.2012.666264] [PMID: 22452318]
[31]
Rakers, C.; Schumacher, F.; Meinl, W.; Glatt, H.; Kleuser, B.; Wolber, G. In silico prediction of human sulfotransferase 1E1 activity guided by pharmacophores from molecular dynamics simulations. J. Biol. Chem., 2016, 291(1), 58-71.
[http://dx.doi.org/10.1074/jbc.M115.685610] [PMID: 26542807]
[32]
Thieker, D.F.; Xu, Y.; Chapla, D.; Nora, C.; Qiu, H.; Felix, T.; Wang, L.; Moremen, K.W.; Liu, J.; Esko, J.D.; Woods, R.J. Downstream products are potent inhibitors of the heparan sulfate 2-O-sulfotransferase. Sci. Rep., 2018, 8(1), 11832.
[http://dx.doi.org/10.1038/s41598-018-29602-4] [PMID: 30087361]
[33]
Kershaw, N.M.; Byrne, D.P.; Parsons, H.; Berry, N.G.; Fernig, D.G.; Eyers, P.A.; Cossticka, R. Structure-based design of nucleoside-derived analogues as sulfotransferase inhibitors. RSC Advances, 2019, 9, 32165-32173.
[http://dx.doi.org/10.1039/C9RA07567D]

Rights & Permissions Print Cite
Article Metrics
19
© 2024 Bentham Science Publishers | Privacy Policy