Isonitrile-based multicomponent synthesis of β-amino boronic acids as β-lactamase inhibitors

[en] The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboronic acids. The corresponding free β-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free β-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D β-lactamase was predicted by a molecular modeling study. © 2020 by the authors.

Disciplines :

Microbiology
Biochemistry, biophysics & molecular biology
Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others

Author, co-author :

Bassini, E.; Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, Milan, 20133, Italy

Gazzotti, S.; Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, Milan, 20133, Italy

Sannio, F.; Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Viale Bracci 16, Siena, 53100, Italy

Presti, L. L.; Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, Milan, 20133, Italy

Sgrignani, J.; Istituto di Ricerca in Biomedicina (IRB), Università della Svizzera Italiana (USI), Via V. Vela 6, Bellinzona, CH-6500, Switzerland

Docquier, Jean-Denis ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines

Grazioso, G.; Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, Milan, 20133, Italy

Silvani, A.; Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, Milan, 20133, Italy

Language :

English

Title :

Isonitrile-based multicomponent synthesis of β-amino boronic acids as β-lactamase inhibitors

Publication date :

2020

Journal title :

Antibiotics

eISSN :

2079-6382

Publisher :

MDPI AG

Special issue title :

Targeting β-lactamases to Fight Bacterial Resistance to β-lactam Antibiotics

Volume :

Issue :

Pages :

1-21

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 13 November 2020

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Bibliography

Marvin Antonio, S.-U. Chemico-Biological Activity and Medicinal Chemistry of Boron-Containing Compounds. Curr. Med. Chem. 2019, 26, 5003–5004, doi:10.2174/092986732626190930142703.
Ban, H.S.; Nakamura, H. Boron-Based Drug Design. Chem. Rec. 2015, 15, 616–635, doi:10.1002/tcr.201402100.
Smoum, R.; Rubinstein, A.; Dembitsky, V.M.; Srebnik, M. Boron containing compounds as protease inhibitors. Chem. Rev. 2012, 112, 4156–4220, doi:10.1021/cr608202m.
Fernandes, G.F.S.; Denny, W.A.; Dos Santos, J.L. Boron in drug design: Recent advances in the development of new therapeutic agents. Eur. J. Med. Chem. 2019, 179, 791–804, doi:10.1016/j.ejmech.2019.06.092.
Zhou, J.; Stapleton, P.; Haider, S.; Healy, J. Boronic acid inhibitors of the class A beta-lactamase KPC-2. Bioorg. Med. Chem. 2018, 26, 2921–2927, doi:10.1016/j.bmc.2018.04.055.
Rojas, L.J.; Taracila, M.A.; Papp-Wallace, K.M.; Bethel, C.R.; Caselli, E.; Romagnoli, C.; Winkler, M.L.; Spellberg, B.; Prati, F.; Bonomo, R.A. Boronic Acid Transition State Inhibitors Active against KPC and Other Class A beta-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design. Antimicrob. Agents Chemother. 2016, 60, 1751–1759, doi:10.1128/aac.02641-15.
Hamrick, J.C.; Docquier, J.D.; Uehara, T.; Myers, C.L.; Six, D.A.; Chatwin, C.L.; John, K.J.; Vernacchio, S.F.; Cusick, S.M.; Trout, R.E.L.; et al. VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine-and Metallo-beta-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2020, 64, doi:10.1128/aac.01963-19.
Lopez, A.; Clark, T.B.; Parra, A.; Tortosa, M. Copper-Catalyzed Enantioselective Synthesis of beta-Boron beta-Amino Esters. Org. Lett. 2017, 19, 6272–6275, doi:10.1021/acs.orglett.7b02784.
Andrés, P.; Ballano, G.; Calaza, M.I.; Cativiela, C. Synthesis of α-aminoboronic acids. Chem. Soc. Rev. 2016, 45, 2291–2307, doi:10.1039/C5CS00886G.
Diaz, D.B.; Scully, C.C.; Liew, S.K.; Adachi, S.; Trinchera, P.; St Denis, J.D.; Yudin, A.K. Synthesis of Aminoboronic Acid Derivatives from Amines and Amphoteric Boryl Carbonyl Compounds. Angew Chem. Int. Ed. Engl. 2016, 55, 12659–12663, doi:10.1002/anie.201605754.
He, Z.; Yudin, A.K. Amphoteric alpha-boryl aldehydes. J. Am. Chem. Soc. 2011, 133, 13770–13773, doi:10.1021/ja205910d.
Tan, J.; Cognetta, A.B., III; Diaz, D.B.; Lum, K.M.; Adachi, S.; Kundu, S.; Cravatt, B.F.; Yudin, A.K. Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors. Nat. Commun. 2017, 8, 1760, doi:10.1038/s41467-017-01319-4.
Adachi, S.; Cognetta, A.B., 3rd; Niphakis, M.J.; He, Z.; Zajdlik, A.; St Denis, J.D.; Scully, C.C.; Cravatt, B.F.; Yudin, A.K. Facile synthesis of borofragments and their evaluation in activity-based protein profiling. Chem. Commun. 2015, 51, 3608–3611, doi:10.1039/c4cc09107h.
Šterman, A.; Sosič, I.; Gobec, S.; Časar, Z. Synthesis of aminoboronic acid derivatives: An update on recent advances. Org. Chem. Front. 2019, 6, 2991–2998, doi:10.1039/C9QO00626E.
Kaldas, S.J.; Rogova, T.; Nenajdenko, V.G.; Yudin, A.K. Modular Synthesis of beta-Amino Boronate Peptidomimetics. J. Org. Chem. 2018, 83, 7296–7302, doi:10.1021/acs.joc.8b00325.
Herrera, R.P.; Marqués-López, E. Multicomponent Reactions: Concepts and Applications for Design and Synthesis, 1st ed.; Wiley: Hoboken, NJ, (USA), 2015.
Rainoldi, G.; Begnini, F.; de Munnik, M.; Lo Presti, L.; Vande Velde, C.M.L.; Orru, R.; Lesma, G.; Ruijter, E.; Silvani, A. Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines. ACS Comb. Sci. 2018, 20, 98–105, doi:10.1021/acscombsci.7b00179.
Lesma, G.; Meneghetti, F.; Sacchetti, A.; Stucchi, M.; Silvani, A. Asymmetric Ugi 3CR on isatin-derived ketimine: Synthesis of chiral 3, 3-disubstituted 3-aminooxindole derivatives. Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141.
Stucchi, M.; Gmeiner, P.; Huebner, H.; Rainoldi, G.; Sacchetti, A.; Silvani, A.; Lesma, G. Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine Receptor Ligand Library. ACS Med. Chem. Lett. 2015, 6, 882–887, doi:10.1021/acsmedchemlett.5b00131.
Stucchi, M.; Cairati, S.; Cetin-Atalay, R.; Christodoulou, M.S.; Grazioso, G.; Pescitelli, G.; Silvani, A.; Yildirim, D.C.; Lesma, G. Application of the Ugi reaction with multiple amino acid-derived components: Synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics. Org. Biomol. Chem. 2015, 13, 4993–5005, doi:10.1039/C5OB00218D.
Lesma, G.; Cecchi, R.; Crippa, S.; Giovanelli, P.; Meneghetti, F.; Musolino, M.; Sacchetti, A.; Silvani, A. Ugi 4-CR/Pictet-Spengler reaction as a short route to tryptophan-derived peptidomimetics. Org. Biomol. Chem. 2012, 10, 9004–9012, doi:10.1039/c2ob26301g.
Silvani, A.; Lesma, G.; Crippa, S.; Vece, V. Multicomponent access to novel dihydroimidazo[1′,5′:1,2]pyrido[3,4-b]indol-2-ium salts and indoles by means of Ugi/Bischler– Napieralski/heterocyclization two step strategy. Tetrahedron 2014, 70, 3994–4001, doi:10.1016/j.tet.2014.04.081.
Lesma, G.; Bassanini, I.; Bortolozzi, R.; Colletto, C.; Bai, R.; Hamel, E.; Meneghetti, F.; Rainoldi, G.; Stucchi, M.; Sacchetti, A., et al. Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues. Org. Biomol. Chem. 2015, 13, 11633–11644, doi:10.1039/c5ob01882j.
Lawrence, K.; Flower, S.E.; Kociok-Kohn, G.; Frost, C.G.; James, T.D. A simple and effective colorimetric technique for the detection of boronic acids and their derivatives. Anal. Meth. 2012, 4, 2215–2217, doi:10.1039/C2AY25346A.
Janvier, P.; Sun, X.; Bienayme, H.; Zhu, J. Ammonium chloride-promoted four-component synthesis of pyrrolo[3,4-b]pyridin-5-one. J. Am. Chem. Soc. 2002, 124, 2560–2567, doi:10.1021/ja017563a.
CCDC 1995920 contains the supplementary crystallographic data for this paper. The Cambridge Crystallographic Data Centre. Available online: www.ccdc.cam.ac.uk/structures.
Knapp, D.M.; Gillis, E.P.; Burke, M.D. A General Solution for Unstable Boronic Acids: Slow-Release Cross-Coupling from Air Stable MIDA Boronates. J. Am. Chem. Soc. 2009, 131, 6961–6963, doi:10.1021/ja901416p.
CCDC 1995919 contains the supplementary crystallographic data for this paper. The Cambridge Crystallographic Data Centre. Available online 14.01.2020: www.ccdc.cam.ac.uk/structures.
Schrödinger Release 2019-4; Maestro, Schrödinger, LLC: New York, NY, USA, 2020.
Bowers, K.J.; Chow, D.E.; Xu, H.; Dror, R.O.; Eastwood, M.P.; Gregersen, B.A.; Klepeis, J.L.; Kolossvary, I.; Moraes, A.; Sacerdoti, D. Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. Proc. ACM/IEEE Conf. Supercomput. 2006, 43, doi:10.1145/1188455.1188544.
Bruker, S. ADABS; Bruker AXS Inc.: Madison, WI, USA, 2008.
Sheldrick, G.M. SHELXT-Integrated Space-group and Crystal-structure Determination. Acta Cryst. 2015, 71, 3–8. doi:10.1107/S2053273314026370
Borgianni, L.; Vandenameele, J.; Matagne, A.; Bini, L.; Bonomo, R.A.; Frere, J.M.; Rossolini, G.M.; Docquier, J.D. Mutational analysis of VIM-2 reveals an essential determinant for metallo-beta-lactamase stability and folding. Antimicrob. Agents Chemother. 2010, 54, 3197–3204, doi:10.1128/aac.01336-09.
Weinstein, M.P. MD M07-Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobicall, 10th ed.; Clinical and Laboratory Standards Institute (CLSI): USA, 2015.
Smith, C.A.; Antunes, N.T.; Stewart, N.K.; Toth, M.; Kumarasiri, M.; Chang, M.; Mobashery, S.; Vakulenko, S.B. Structural basis for carbapenemase activity of the OXA-23 beta-lactamase from Acinetobacter baumannii. Chem. Biol. 2013, 20, 1107–1115, doi:10.1016/j.chembiol.2013.07.015.
Wang, X.; Minasov, G.; Shoichet, B.K. Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs. J. Mol. Biol. 2002, 320, 85–95, doi:10.1016/s0022-2836(02)00400-x.
Sgrignani, J.; Grazioso, G.; De Amici, M. Insight into the Mechanism of Hydrolysis of Meropenem by OXA-23 Serine-beta-lactamase Gained by Quantum Mechanics/Molecular Mechanics Calculations. Biochemistry 2016, 55, 5191–5200, doi:10.1021/acs.biochem.6b00461.
Jorgensen, W.L.; Chandrasekhar, J.; Madura, J.D.; Impey, R.W.; Klein, M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926–935, doi:10.1063/1.445869.
Roos, K.; Wu, C.; Damm, W.; Reboul, M.; Stevenson, J.M.; Lu, C.; Dahlgren, M.K.; Mondal, S.; Chen, W.; Wang, L., et al. OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules. J. Chem. Theory Comput. 2019, 15, 1863–1874, doi:10.1021/acs.jctc.8b01026.
Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14, 33– 38, doi:10.1016/0263-7855(96)00018-5.
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 2006, 49, 6177–6196, doi:10.1021/jm051256o.

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