Synthesis and Biological Evaluation of a Highly Constrained Analogue of Methylthioadenosine (MTA)

Gustavo Senra G. de Carvalho, Rafael Mafra de P. Dias, Jean-Louis Fourrey, Vânia L. Silva, Cláudio G. Diniz, Adilson D. da Silva

Departamento de Parasitologia Microbiologia e Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Juiz de Fora, Juiz de Fora-MG, Brasil.
Departamento de Química, Instituto de Ciências Exatas (ICE), Universidade Federal de Juiz de Fora, Juiz de Fora-MG, Brasil.
Institut de Chimie des Substances Naturelles, Gif-sur-Yvette Cedex, France.

DOI: 10.4236/ijoc.2012.24055                

Abstract

We describe the synthesis and the antibacterial evaluation 2’,N³-cyclonucleoside 3 analogue of MTA that is characterized by the presence of an additional linkage between the heterocyclic ring and the sugar moiety.

Keywords

Synthesis; Biological Evaluation; Antibacterial; Analogue Methylthioadenosine

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	E. Tacconelli, G. De Angelis, M. A. Cataldo, E. Pozzi and R. Cauda, “Does Antibiotic Exposure Increase the Risk of Methicillin-Resistant Staphylococcus Aureus (MRSA) Isolation? A Systematic Review and Meta-Analysis,” Journal of Antimicrobial Chemotherapy, Vol. 61, No. 1, 2008, pp. 26-38. doi:10.1093/jac/dkm416
[2]	D. M. Drekonja, L. M. Traynor, D. Decarolis, K. B. Crossley and J. R. Johnson, “Treatment of Non-Life-Threatening Methicillin-Resistant Staphylococcus Aureus Infections with Alternative Antimicrobial Agents: A 2-Year Retrospective Review,” Diagnostic Microbiology and Infectious Disease, Vol. 63, No. 2, 2009, pp. 201-207. doi:10.1016/j.diagmicrobio.2008.10.001
[3]	H. W. Boucher, G. H. Talbot, J. S. Bradley, J. E. Edwards Jr., D. Gilbert, L. B. Rice, M. Scheld, B. Spellberg and J. Bartlet, “Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America,” Clinical Infectious Disease, Vol. 48, No. 1, 2009, pp. 1-12. doi:10.1086/595011
[4]	M. K. Riscoe, A. J. Ferro and J. H. Fitchen, “Methionine Recycling as a Target for Antiprotozoal Drug Development,” Parasitology Today, Vol. 5, No. 10, 1989, pp. 330-333. doi:10.1016/0169-4758(89)90128-2
[5]	M. P. Barrett, J. C. Mottram and G. H. Coombs, “Recent Advances in Identifying and Validating Drug Targets in Trypanosomes and Leishmanias,” Trends in Microbiology, Vol. 7, No. 2, 1999, pp. 82-88. doi:10.1016/S0966-842X(98)01433-4
[6]	P. A. Michels, F. Bringaud, M. Herman and V. Hannaert, “Metabolic Functions of Glycosomes in Trypanosomatids,” Biochimica et Biophysica Acta, Vol. 1763, No. 12, 2006, pp. 1463-1477. doi:10.1016/j.bbamcr.2006.08.019
[7]	J. F. Barrett, J. A. Sutcliffe and T. D. Gootz, “In Vitro Assays Used to Measure the Activity of Topoisomerases,” Antimicrobial Agents and Chemotherapy, Vol. 34, No. 1, 1990, pp. 1-7. doi:10.1128/AAC.34.1.1
[8]	M. H. El Kouni, “Potential Chemotherapeutic Targets in the Purine Metabolism of Parasites,” Pharmacolology & Therapeutics, Vol. 99, No. 3, 2003, pp. 283-309. doi:10.1016/S0163-7258(03)00071-8
[9]	S. Muller, E. Liebau, R. D. Walter and R. L. Krauth-Siegel, “Thiol-Based Redox Metabolism of Protozoan Parasites,” Trends in Parasitology, Vol. 19, No. 7, 2003, pp. 320-328. doi:10.1016/S1471-4922(03)00141-7
[10]	C. H. Miller and J. A. Duerre, “S-Ribosylhomocysteine Cleavage Enzyme from Escherichia coli,” Journal of Biological Chemistry, Vol. 243, No. 1, 1968, pp. 92-97.
[11]	W. A. M. Loenen, “S-adenosylmethionine: Jack of All Trades and Master of Everything?” Biochemical Society Transactions, Vol. 34, No. 2, 2006, pp. 330-333. doi:10.1042/BST20060330
[12]	M. Fontecave, M. Atta and E. Mulliez, “S-Adenosylmethionine: Nothing Goes to Waste,” Trends in Biochemical Science, Vol. 29, No. 5, 2004, pp. 243-249. doi:10.1016/j.tibs.2004.03.007
[13]	J. E. Lee, E. C. Settembre, K. A. Cornell, M. K. Riscoe, J. R. Sufrin, S. E. Ealick and P. L. Howell, “Structural Comparison of MTA Phosphorylase and MTA/AdoHcy Nucleosidase Explains Substrate Preferences and Identifies Regions Exploitable for Inhibitor Design,” Biochemistry, Vol. 43, No. 18, 2004, pp. 5159-5169.
[14]	M. E. Tedder, Z. Nie, S. Margosiak, S. Chu, V. A. Feher, R. Almassy, K. Appelt and K. M. Yager, “Structure-Based Design, Synthesis, and Antimicrobial Activity of Purine Derived SAH/MTA Nucleosidase Inhibitors,” Bioorganic and Medicinal Chemistry, Vol. 14, No. 12, 2004, pp. 3165-3168. doi:10.1016/j.bmcl.2004.04.006
[15]	V. Singh, G. B. Evans, D. H. Lenz, J. M. Mason, K. Clinch, S. Mee, G. F. Painter, P. C. Tyler, R. H. Furneaux, J. E. Lee, P. L. Howell and V. L. Schramm, “Femtomolar Transition State Analogue inhibitors of 5’-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Escherichia coli,” Journal of Biological Chemistry, Vol. 280, No. 18, 2005, pp. 18265-18273. doi:10.1074/jbc.M414472200
[16]	A. Mieczkowski, V. Roy and L. A. Agrofoglio, “Preparation of Cyclonucleosides,” Chemical Reviews, Vol. 110, No. 4, 2010, pp. 1828-1856.
[17]	A. Mieczkowski and L. A. Agrofoglio, “Potential and Perspectives of Cyclonucleosides,” Current Medicinal Chemistry, Vol. 17, No. 15, 2010, pp. 1527-1549. doi:10.2174/092986710790979962
[18]	G. S. G. de Carvalho, J.-L. Fourrey, R. H. Dodd and A. D. da Silva, “Synthesis of a 4’,4’-Spirothietane-2’,N3-cycloadenosine as a Highly Constrained Analogue of 5'-Deoxy-5'-methylthioadenosine (MTA),” Tetrahedron Letters, Vol. 50, No. 4, 2009, pp. 463-466. doi:10.1016/j.tetlet.2008.11.039
[19]	D. R. Stalons and C. Thornsberry, “Broth-Dilution Method for Determining the Antibiotic Susceptibility of Anaerobic Bacteria,” Antimicrobial Agents and Chemotherapy, Vol. 7, No. 1, 1975, pp. 15-21. doi:10.1128/AAC.7.1.15
[20]	I. Zlatev, J.-L. Vasseur and F. Morvan, “Deoxygenation of 5-O-benzoyl-1,2-isopropylidene-3-O-imidazolylthiocarbonyl-α-D-xylofuranose Using Dimethyl Phosphite: An Efficient Alternate Method towards a 3’-Deoxynucleoside Glycosyl Donor,” Tetrahedron Letters, Vol. 49, No. 20, 2008, pp. 3288-3290. doi:10.1016/j.tetlet.2008.03.079