First virtual screening and experimental validation of inhibitors targeting GES-5 carbapenemase

Journal of Computer-Aided Molecular Design - Tập 33 Số 2 - Trang 295-305 - 2019
Francesca Spyrakis1, Pierangelo Bellio2, Antonio Quotadamo3, Pasquale Linciano3, Paolo Benedetti4, Giulia D’Arrigo1, Massimo Baroni5, Laura Cendron6, Giuseppe Celenza2, Donatella Tondi3
1Department of Drug Science and Technology, University of Turin, Via Giuria 9, 10125, Turin, Italy
2Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, via Vetoio 1, 67100, L’Aquila, Italy
3Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy
4Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto, 8, 06123 Perugia, Italy
5Molecular Discovery Limited, U.501 Centennial Park, Centennial Ave, Elstree, Borehamwood, Hertfordshire, WD6 3FG, UK
6Department of Biology, University of Padua, Viale G. Colombo 3, 35121 Padua, Italy

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Tondi D, Cross S, Venturelli A et al (2016) Decoding the structural basis for carbapenem hydrolysis by class A β-lactamases: fishing for a pharmacophore. Curr Drug Targets 17:983–1005. https://doi.org/10.2174/1389450116666151001104448

Cantón R, Akóva M, Carmeli Y et al (2012) Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clin Microbiol Infect 18:413–431. https://doi.org/10.1111/j.1469-0691.2012.03821.x

Naas T, Poirel L, Nordmann P (2008) Minor extended-spectrum beta-lactamases. Clin Microbiol Infect. https://doi.org/10.1111/j.1469-0691.2007.01861.x

Weldhagen GF (2006) Genetic stability of class 1 integron-borne blaGES-type genes under short-term in vitro antibiotic stress. Int J Antimicrob Agents 28:481–483. https://doi.org/10.1016/j.ijantimicag.2006.08.012

Smith CA, Nossoni Z, Toth M et al (2016) Role of the conserved disulfide bridge in class A carbapenemases. J Biol Chem 291:22196–22206. https://doi.org/10.1074/jbc.M116.749648

Smith CA, Frase H, Toth M et al (2012) Structural basis for progression toward the carbapenemase activity in the GES family of β-lactamases. J Am Chem Soc 134:19512–19515. https://doi.org/10.1021/ja308197j

Stewart NK, Smith CA, Frase H et al (2015) Kinetic and structural requirements for carbapenemase activity in GES-type β-lactamases. Biochemistry 54:588–597. https://doi.org/10.1021/bi501052t

Chihi H, Bonnin RA, Bourouis A et al (2016) GES-11-producing Acinetobacter baumannii clinical isolates from Tunisian hospitals: long-term dissemination of GES-type carbapenemases in North Africa. J Glob Antimicrob Resist 5:47–50. https://doi.org/10.1016/j.jgar.2016.03.005

Bonnin RA, Jousset AB, Urvoy N et al (2017) Detection of GES-5 carbapenemase in Klebsiella pneumoniae, a newcomer in France. Antimicrob Agents Chemother 61:e02263–e02216. https://doi.org/10.1128/AAC.02263-16

Poirel L, Le Thomas I, Naas T et al (2000) Biochemical sequence analyses of GES-1, a novel class A extended-spectrum beta-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. Antimicrob Agents Chemother 44:622–632. https://doi.org/10.1128/AAC.44.3.622-632.2000

http://bldb.eu/BLDB.php?prot=A#GES . Accessed July 2018

Pedersen T, Sekyere JO, Govinden U et al (2018) Spread of plasmid-encoded NDM-1 and GES-5 carbapenemases among extensively drug-resistant and pandrug-resistant clinical enterobacteriaceae in durban, South Africa. Antimicrob Agents Chemother 62:e02178–e02117. https://doi.org/10.1128/AAC.02178-17

Castillo-Vera J, Ribas-Aparicio RM, Nicolau CJ et al (2012) Unusual diversity of acquired β-lactamases in multidrug-resistant Pseudomonas aeruginosa Isolates in a Mexican Hospital. Microb Drug Resist 18:471–478. https://doi.org/10.1089/mdr.2011.0183

Viedma E, Juan C, Acosta J et al (2009) Nosocomial spread of colistin-only-sensitive sequence type 235 Pseudomonas aeruginosa isolates producing the extended-spectrum β-lactamases GES-1 and GES-5 in Spain. Antimicrob Agents Chemother 53:4930–4933. https://doi.org/10.1128/AAC.00900-09

Smith CA, Caccamo M, Kantardjieff KA, Vakulenko S (2007) Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum β-lactamases. Acta Crystallogr D 63:982–992. https://doi.org/10.1107/S0907444907036955

Santucci M, Spyrakis F, Cross S et al (2017) Computational and biological profile of boronic acids for the detection of bacterial serine- and metallo-β-lactamases. Sci Rep 7:17716. https://doi.org/10.1038/s41598-017-17399-7

Spyrakis F, Celenza G, Marcoccia F et al (2017) Structure-based virtual screening for the discovery of novel inhibitors of New Delhi metallo-β-lactamase-1. ACS Med Chem Lett 9:45–50. https://doi.org/10.1021/acsmedchemlett.7b00428

Baroni M, Cruciani G, Sciabola S et al (2007) A common reference framework for analyzing/comparing proteins and ligands. fingerprints for ligands and proteins (FLAP): theory and application. J Chem inf Model 47:279–294. https://doi.org/10.1021/ci600253e

Spyrakis F, Cellini B, Bruno S et al (2014) Targeting cystalysin, a virulence factor of Treponema denticola-supported periodontitis. ChemMedChem 9:1501–1511. https://doi.org/10.1002/cmdc.201300527

Spyrakis F, Singh R, Cozzini P et al (2013) Isozyme-specific ligands for O-acetylserine sulfhydrylase, a novel antibiotic target. PLoS ONE 8:e77558. https://doi.org/10.1371/journal.pone.0077558

Milletti F, Storchi L, Goracci L et al (2010) Extending pKa prediction accuracy: high-throughput pK a measurements to understand pKa modulation of new chemical series. Eur J Med Chem 45:4270–4279. https://doi.org/10.1016/j.ejmech.2010.06.026

Spyrakis F, Felici P, Bayden AS et al (2013) Fine tuning of the active site modulates specificity in the interaction of O-acetylserine sulfhydrylase isozymes with serine acetyltransferase. Biochim Biophys Acta: Proteins Proteom 1834:169–181. https://doi.org/10.1016/j.bbapap.2012.09.009

Wade RC, Goodford PJ (1989) The role of hydrogen-bonds in drug binding. Prog Clin Biol Res 289:433–444. https://doi.org/10.1007/0-387-29148-2_2

Quotadamo A, Linciano P, Davoli P et al (2016) An improved synthesis of CENTA, a chromogenic substrate for β-lactamases. Synlett 27:2447–2450. https://doi.org/10.1055/s-0035-1562454

Feng BY, Shoichet BK (2006) A detergent-based assay for the detection of promiscuous inhibitors. Nat Protoc 1:550–553. https://doi.org/10.1038/nprot.2006.77

Yung-Chi C, Prusoff WH (1973) Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108. https://doi.org/10.1016/0006-2952(73)90196-2

Spyrakis F, Benedetti P, Decherchi S et al (2015) A pipeline to enhance ligand virtual screening: integrating molecular dynamics and fingerprints for ligand and proteins. J Chem Inf Model 26:2256–2274. https://doi.org/10.1021/acs.jcim.5b00169

Krishnan NP, Nguyen NQ, Papp-Wallace KM et al (2015) Inhibition of Klebsiella β-lactamases (SHV-1 and KPC-2) by avibactam: a structural study. PLoS ONE 10:e0136813. https://doi.org/10.1371/journal.pone.0136813

Celenza G, Vicario M, Bellio P et al (2018) Phenylboronic acid derivatives as validated leads active in clinical strains overexpressing KPC-2: a step against bacterial resistance. ChemMedChem 13:713–724. https://doi.org/10.1002/cmdc.201700788

Tondi D, Venturelli A, Bonnet R et al (2014) Targeting class A and C serine β-lactamases with a broad-spectrum boronic acid derivative. J Med Chem 57:5449–5458. https://doi.org/10.1021/jm5006572

Farina D, Spyrakis F, Venturelli A et al (2014) The inhibition of extended spectrum β-lactamases: hits and leads. Curr Med Chem 21:1405–1434. https://doi.org/10.2174/09298673113206660323

Genovese F, Lazzari S, Venturi E et al (2017) Design, synthesis and biological evaluation of non-covalent AmpC β-lactamases inhibitors. Med Chem Res 26:975–986. https://doi.org/10.1007/s00044-017-1809-x

Klein R, Linciano P, Celenza G et al (2018) In silico identification and experimental validation of hits active against KPC-2 β-lactamase. PLoS ONE 13:e0203241. https://doi.org/10.1371/journal.pone.0203241

Strynadka NCJ, Adachi H, Jensen SE et al (1992) Molecular structure of the acyl-enzyme intermediate in β-lactam hydrolysis at 1.7 Å resolution. Nature 359:700–705. https://doi.org/10.1038/359700a0

Swarén P, Maveyraud L, Raquet X et al (1998) X-ray analysis of the NMC-A beta-lactamase at 1.64-A resolution, a class A carbapenemase with broad substrate specificity. J Biol Chem 273:26714–26721. https://doi.org/10.1074/JBC.273.41.26714

Sougakoff W, L’Hermite G, Pernot L et al (2002) Structure of the imipenem-hydrolyzing class A β-lactamase SME-1 from Serratia marcescens. Acta Crystallogr D 58:267–274. https://doi.org/10.1107/S0907444901019606

Fonseca F, Chudyk EI, Van Der Kamp MW et al (2012) The basis for carbapenem hydrolysis by class a beta-lactamases: a combined investigation using crystallography and simulations. J Am Chem Soc 134:18275–18285. https://doi.org/10.1021/ja304460j

Babaoglu K, Simconov A, Irwin JJ et al (2008) Comprehensive mechanistic analysis of hits from high-throughput and docking screens against β-lactamase. J Med Chem 51:2502–2511. https://doi.org/10.1021/jm701500e

Tondi D, Morandi F, Bonnet R et al (2005) Structure-based optimization of a non-beta-lactam lead results in inhibitors that do not up-regulate beta-lactamase expression in cell culture. J Am Chem Soc 127:4632–4639. https://doi.org/10.1021/ja042984o

Zhu T, Cao S, Su PC et al (2013) Hit identification and optimization in virtual screening: practical recommendations based on a critical literature analysis. J Med Chem 56:6560–6572. https://doi.org/10.1021/jm301916b

Balakin KV, Savchuk NP, Tetko IV (2006) In silico approaches to prediction of aqueous and DMSO solubility of drug-like compounds: trends, problems and solutions. Curr Med Chem 13:223–241. https://doi.org/10.2174/092986706775197917

Tondi D, Powers RA, Caselli E et al (2001) Structure-based design and in-parallel synthesis of inhibitors of AmpC β-lactamase. Chem Biol 8:593–611. https://doi.org/10.1016/S1074-5521(01)00034-5

Venturelli A, Tondi D, Cancian L et al (2007) Optimizing cell permeation of an antibiotic resistance inhibitor for improved efficacy. J Med Chem 50:5644–5654. https://doi.org/10.1021/jm070643q

Tondi D, Calò S, Shoichet BK, Costi MP (2010) Structural study of phenyl boronic acid derivatives as AmpC β-lactamase inhibitors. Bioorg Med Chem Lett 20:3416–3419. https://doi.org/10.1016/j.bmcl.2010.04.007