TBU Publications
Repository of TBU Publications

Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones

DSpace Repository

Show simple item record


dc.title Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones en
dc.contributor.author de Macedo, Maíra Bidart
dc.contributor.author Kimmel, Roman
dc.contributor.author Urankar, Damijana
dc.contributor.author Gazvoda, Martin
dc.contributor.author Peixoto, Antonio
dc.contributor.author Cools, Freya
dc.contributor.author Torfs, Eveline
dc.contributor.author Verschaeve, Luc
dc.contributor.author Lima, Emerson Silva
dc.contributor.author Lyčka, Antonín
dc.contributor.author Milićević, David
dc.contributor.author Klásek, Antonín
dc.contributor.author Cos, Paul
dc.contributor.author Kafka, Stanislav
dc.contributor.author Košmrlj, Janez
dc.contributor.author Cappoen, Davie
dc.relation.ispartof European Journal of Medicinal Chemistry
dc.identifier.issn 0223-5234 Scopus Sources, Sherpa/RoMEO, JCR
dc.date.issued 2017
utb.relation.volume 138
dc.citation.spage 491
dc.citation.epage 500
dc.type article
dc.language.iso en
dc.publisher Elsevier Masson SAS
dc.identifier.doi 10.1016/j.ejmech.2017.06.061
dc.relation.uri https://www.sciencedirect.com/science/article/pii/S0223523417305159
dc.subject Mycobacterium tuberculosis en
dc.subject Tuberculosis en
dc.subject 4-Hydroxyquinolin-2(1H)-ones en
dc.subject Antibiotic en
dc.subject Cytotoxicity en
dc.subject Genotoxicity en
dc.description.abstract In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 μM and against Mycobacterium bovis AN5A below 15 μM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox™ assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 μM and a CC50 against MRC-5 of 67.4 μM. © 2017 Elsevier Masson SAS en
utb.faculty Faculty of Technology
dc.identifier.uri http://hdl.handle.net/10563/1007208
utb.identifier.obdid 43876735
utb.identifier.scopus 2-s2.0-85021723786
utb.identifier.wok 000411297000039
utb.identifier.pubmed 28689097
utb.identifier.coden EJMCA
utb.source j-scopus
dc.date.accessioned 2017-09-03T21:40:00Z
dc.date.available 2017-09-03T21:40:00Z
dc.description.sponsorship CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; 11912/13-8, MEC, Ministério da Educação; 12N5915N, FWO, Fonds Wetenschappelijk Onderzoek; P1-0230, ARRS, Javna Agencija za Raziskovalno Dejavnost RS
dc.description.sponsorship Research Foundation Flanders (FWO-Vlaanderen) [12N5915N]; Brazilian Federal Agency; Evaluation of Graduate Education (CAPES) within the Ministry of Education of Brazil [11912/13-8]; Slovenian Research Agency [P1-0230]; TBU in Zlin [IGA/FT/2017/005]
utb.contributor.internalauthor Kimmel, Roman
utb.contributor.internalauthor Milićević, David
utb.contributor.internalauthor Klásek, Antonín
utb.contributor.internalauthor Kafka, Stanislav
utb.fulltext.affiliation Maíra Bidart de Macedo a , Roman Kimmel b , Damijana Urankar c , Martin Gazvoda c , Antonio Peixoto d, e , Freya Cools a , Eveline Torfs a , Luc Verschaeve f , Emerson Silva Lima g , Antonín Lyčcka h , David Milićević b , Antonín Klásek b , Paul Cos a , Stanislav Kafka b, * , Janez Košmrlj c, ** , Davie Cappoen a, *** a Laboratory of Microbiology, Parasitology and Hygiene (LMPH), S7, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium b Faculty of Technology, Tomas Bata University, Vavrečkova 275, CZ-760 01 Zlín, Czech Republic c Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia d Centre National de la Recherche Scientifique, IPBS, UMR 5089, F-31077 Toulouse, France e Univ. Toulouse, UPS, F-31000 Toulouse, France f Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium g Faculty of Pharmaceutical Sciences, Federal Univeristy of Amazonas, Avenida General Rodrigo Octavio Campo de Jordão, 6200, Coroado, Manaus 69077-000, Amazonas, Brazil h Faculty of Science, University of Hradec Králové, Rokitanského 62, CZ-500 03 Hradec Králové III, Czech Republic * Corresponding author. ** Corresponding author. *** Corresponding author. E-mail addresses: Kafka@ft.utb.cz (S. Kafka), Janez.Kosmrlj@fkkt.uni-lj.si (J. Košmrlj), Davie.Cappoen@uantwerpen.be (D. Cappoen).
utb.fulltext.dates Received 30 April 2017 Received in revised form 16 June 2017 Accepted 28 June 2017 Available online 29 June 2017
utb.fulltext.references [1] WHO, Global Tuberculosis Report, 2016, p. 2016. [2] A. Zumla, P. Nahid, S.T. Cole, Advances in the development of new tuberculosis drugs and treatment regimens, Nat. Rev. Drug Discov. 12 (2013) 388e404. [3] J. Paeshuyse, I. Vliegen, L. Coelmont, P. Leyssen, O. Tabarrini, P. Herdewijn, H. Mittendorfer, J. Easmon, V. Cecchetti, R. Bartenschlager, G. Puerstinger, J. Neyts, Comparative in vitro anti-hepatitis C virus activities of a selected series of polymerase, protease, and helicase inhibitors, Antimicrob. Agents Chemother. 52 (2008) 3433e3437. [4] M.L. Barreca, G. Manfroni, P. Leyssen, J. Winquist, N. Kaushik-Basu, J. Paeshuyse, R. Krishnan, N. Iraci, S. Sabatini, O. Tabarrini, A. Basu, U.H. Danielson, J. Neyts, V. Cecchetti, Structure-based discovery of pyrazolobenzothiazine derivatives as inhibitors of hepatitis C virus replication, J. Med. Chem. 56 (2013) 2270e2282. [5] J. de Vicente, R.T. Hendricks, D.B. Smith, J.B. Fell, J. Fischer, S.R. Spencer, P.J. Stengel, P. Mohr, J.E. Robinson, J.F. Blake, R.K. Hilgenkamp, C. Yee, G. Adjabeng, T.R. Elworthy, J. Tracy, E. Chin, J. Li, B. Wang, J.T. Bamberg, R. Stephenson, C. Oshiro, S.F. Harris, M. Ghate, V. Leveque, I. Najera, S. Le Pogam, S. Rajyaguru, G. Ao-Ieong, L. Alexandrova, S. Larrabee, M. Brandl, A. Briggs, S. Sukhtankar, R. Farrell, B. Xu, Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: synthesis and structureeactivity relationships of benzothiazine-substituted quinolinediones, Bioorg. Med. Chem. Lett. 19 (2009) 3642e3646. [6] R.T. Hendricks, J.B. Fell, J.F. Blake, J.P. Fischer, J.E. Robinson, S.R. Spencer, P.J. Stengel, A.L. Bernacki, V.J.P. Leveque, S. Le Pogam, S. Rajyaguru, I. Najera, J.A. Josey, J.R. Harris, S. Swallow, Non-nucleoside inhibitors of HCV NS5B polymerase. Part 1: synthetic and computational exploration of the binding modes of benzothiadiazine and 1,4-benzothiazine HCV NS5b polymerase inhibitors, Bioorg. Med. Chem. Lett. 19 (2009) 3637e3641. [7] R. Tedesco, D. Chai, M.G. Darcy, D. Dhanak, D.M. Fitch, A. Gates, V.K. Johnston, R.M. Keenan, J. Lin-Goerke, R.T. Sarisky, A.N. Shaw, K.L. Valko, K.J. Wiggall, M.N. Zimmerman, K.J. Duffy, Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors, Bioorg. Med. Chem. Lett. 19 (2009) 4354e4358. [8] J. Deng, T. Sanchez, L.Q. Al-Mawsawi, R. Dayam, R.A. Yunes, A. Garofalo, M.B. Bolger, N. Neamati, Discovery of structurally diverse HIV-1 integrase inhibitors based on a chalcone pharmacophore, Bioorg. Med. Chem. 15 (2007) 4985e5002. [9] A.-G.A. El-Agamey, A.A. Abo Attaia, Synthesis and study of antimicrobial agents of newly 6-nitro-4-hydroxy-2-quinolone derivatives, Arch. Appl. Sci. Res. 4 (2012) 1339e1344. [10] V. Sebastian, M.-T. Manoli, D.I. Perez, C. Gil, E. Mellado, A. Martinez, E.A. Espeso, N.E. Campillo, New applications for known drugs: human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth, Eur. J. Med. Chem. 116 (2016) 284e289. [11] K. Arya, M. Agarwal, Microwave prompted multigram synthesis, structural determination, and photo-antiproliferative activity of fluorinated 4-hydroxyquinolinones, Bioorg. Med. Chem. Lett. 17 (2007) 86e93. [12] (a) P. Baumgarten, W. Kärgel, A new synthesis of 2,4-dihydroxyquinolines, Ber. Dtsch. Chem. Ges. 60 (1927) 832e842; (b) R.G. Cooke, H.F. Haynes, The alkaloids of Evodia littoralis, Aust. J. Chem. 7 (1954) 273e276; (c) H. Rapoport, K.G. Holden, Isolation of alkaloids from Balfourodendron riedelianum. The structure of balfourodine, J. Am. Chem. Soc. 81 (1959) 3738e3743; (d) W. Stadlbauer, O. Schmut, T. Kappe, Synthesis of benzofurans by cyclodehydrogenation of phenylmalonyl heterocyclics, Monatsh. Chem. 111 (1980) 1005e1013; (e) W. Stadlbauer, T. Kappe, Oxidative hydroxylation of heterocyclic β-dicar-bonyl compounds, Monatsh. Chem. 116 (1985) 1005e1015. [13] S. Kafka, A. Klásek, J. Košmrlj, Novel ring contraction of 3-hydroxy-2,4(1H,3H)-quinolinediones in aqueous alkali. The first convenient route to 2-hydroxyindoxyls, J. Org. Chem. 66 (2001) 6394e6399. [14] W. Stadlbauer, R. Laschober, T. Kappe, Palladium-catalyzed ring closure reactions to benzofurans: a new and effective approach to azacoumestrols, Liebigs Ann. Chem. (1990) 531e539. [15] V. Ioffe, K. Ulanenko, A. Laxer, M. Safadi, D. Licht, I. Lovinger, U.T. Fristed, N-Ethyl-N-phenyl-1,2-dihydro-4,5-dihydroxy-1-methyl-2-oxo-3-quinolinecarboxamide, preparation and uses thereof, U.S. Pat. Appl. Publ. (August 22, 2013). US2013/0217724. [16] S. Kafka, R. Aigner, T. Kappe, Reaction of malonates with camphoranile. Synthesis of 4-hydroxy-2-pyridones attached to the bornane ring system, J. Heterocycl. Chem. 43 (2006) 1105e1109. [17] O. Sperandio, J.B. Baell, M.A. Miteva, B.O. Villoutreix, FAF-Drugs3: a web server for compound property calculation and chemical library design, Nucleic Acids Res. 43 (W1) (2015) W200eW207. [18] F. Cheng, W. Li, Y. Zhou, J. Shen, Z. Wu, G. Liu, P.W. Lee, Y. Tang, AdmetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties, J. Chem. Inf. Model 52 (2012) 3099e3105. [19] D. Cappoen, P. Claes, J. Jacobs, R. Anthonissen, V. Mathys, L. Verschaeve, K. Huygen, N. De Kimpe, 1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis, J. Med. Chem. 57 (2014) 2895e2907. [20] G. Repetto, A. del Peso, J.L. Zurita, Neutral red uptake assay for the estimation of cell viability/cytotoxicity, Nat. Protoc. 3 (2008) 1125e1131. [21] S. Kafka, K. Proisl, V. Kašpárková, D. Urankar, R. Kimmel, J. Košmrlj, Oxidative ring opening of 3-hydroxyquinolin-2(1H)-ones into N-( a -ketoacyl)anthranilic acids, Tetrahedron 69 (2013) 10826e10835. [22] I.V. Ukrainets, S.G. Taran, O.A. Evtifeeva, O.V. Gorokhova, P.A. Bezugly, A.V. Turov, L.N. Voronina, N.I. Filimonova, 4-Hydroxy-2-quinolones. 19. New synthesis of 3-alkyl-2-oxo-4-hydroxyquinolines, Chem. Heterocycl. Compd. (N. Y., N. Y. U. S.) 30 (1994) 591e595. Khim. Geterotsikl. Soedin. (1994) 673e678. [23] A. Klásek, A. Lyčka, F. Křemen, M. Rouchal, Stereochemistry of the reduction of a -chloroketones with sodium borohydride-application to 3-chloroquinoline-2,4-diones, Tetrahedron 72 (2016) 4490e4497. L.C. Zikou, O. Igglessi-Markopoulou, Modified Mukaiyama reaction for the synthesis of quinoline alkaloid analogues: total synthesis of 3,3-diisopentenyl-N-methylquinoline-2,4-dione, Synthesis (2008) 1861e1866. [25] W. Stadlbauer, R. Laschober, H. Lutschounig, G. Schindler, T. Kappe, Organic azides in heterocycle synthesis. Part 16. Halogenation reactions in position 3 of quinoline-2,4-dione systems by electrophilic substitution and halogen exchange, Monatsh. Chem. 123 (1992) 617e636. [26] A. Klásek, V. Mrkvička, A. Pevec, J. Košmrlj, Novel tandem hydration/cyclo-dehydration of a -thiocyanatoketones to 2-oxo-3-thiazolines. Application to thiazolo[5,4-c]quinoline-2,4(3aH,5H)-dione synthesis, J. Org. Chem. 69 (2004) 5646e5651. [27] E. Ziegler, H. Junek, Synthesis of heterocycles. XXII. Synthesis of 4-hydroxycarbostyril and its derivatives, Monatsh. Chem. 90 (1959) 762e767. [28] A. Klásek, K. Kořistek, S. Kafka, J. Košmrlj, Thermal rearrangement of 3-hydroxy-1H,3H-quinoline-2,4-diones to 3-acyloxy-2,3-dihydro-1H-indol-2-ones, Heterocycles 60 (2003) 1811e1820. [29] S. Kafka, A. Klásek, J. Polis, J. Košmrlj, Syntheses of 3-aminoquinoline-2,4(1H,3H)-diones, Heterocycles 57 (2002) 1659e1682. [30] G.A. Freeman III, C.W. Andrews III, A.L. Hopkins, G.S. Lowell, L.T. Schaller, J.R. Cowan, S.S. Gonzales, G.W. Koszalka, R.J. Hazen, L.R. Boone, R.G. Ferris, K.L. Creech, G.B. Roberts, S.A. Short, K. Weaver, D.J. Reynolds, J. Ren, D.I. Stuart, D.K. Stammers, J.H. Chan, Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2, J. Med. Chem. 47 (2004) 5923e5936. [31] A. Klásek, K. Kořistek, J. Polis, J. Košmrlj, Synthesis of novel 3-acyloxy-1,3-dihydro-2H-indol-2-ones and isomeric 4-acyl-1,4-dihydro-3,1-benzoxazin-2-ones: double rearrangement of 3-hydroxyquinolin-2(1H)-ones, Tetrahedron 56 (2000) 1551e1560. [32] W.M.F. Fabian, K.S. Niederreiter, G. Uray, W. Stadlbauer, Substituent effects on absorption and fluorescence spectra of carbostyrils, J. Mol. Struct. 477 (1999) 209e220. [33] T. Ishida, S. Kikuchi, T. Yamada, Efficient preparation of 4-hydroxyquinolin-2(1H)-one derivatives with silver-catalyzed carbon dioxide incorporation and intramolecular rearrangement, Org. Lett. 15 (2013) 3710e3713. [34] H. Nishimura, Y. Nagai, T. Suzuki, T. Sawayama, Synthesis of 4-hydroxy-2(1H)-quinolone derivatives, Yakugaku Zasshi 90 (1970) 818e828. Chem. Abstr. 73 (1970) 77020. [35] T. Kappe, G. Korbuly, E. Pongratz, Ylides of heterocycles. IV. Sulfonium and pyridinium ylides of coumarin and 2-quinolone, Monatsh. Chem. 114 (1983) 303e315. [36] T. Ohta, Y. Mori, Synthesis of 3-alkyl-4-hydroxycarbostyrils, Yakugaku Zasshi 75 (1955) 1162e1164. Chem. Abstr. 50 (1956) 7802. [37] T. Ohta, Furoquinolines. I. Catalytic reduction of dictamnine and skimmianine, Yakugaku Zasshi 73 (1953) 63e66. Chem. Abstr. 47 (1953) 63e66. [38] N.J. McCorkindale, Intensities of the carbonyl bands in the infrared spectra of 2- and 4-quinolones, Tetrahedron 14 (1961) 223e229. [39] M.A. Miteva, S. Violas, M. Montes, D. Gomez, P. Tuffery, B.O. Villoutreix, FAF-drugs: free ADME/tox filtering of compound collections, Nucleic Acids Res. 34 (2006) 738e744. [40] QikProp, Version 3.2, Schrodinger LLC, New York, 2009.
utb.fulltext.sponsorship This work was partially supported by the Research Foundation Flanders (FWO-Vlaanderen) DC: Fellowship 12N5915N. The authors acknowledge the financial support from the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) within the Ministry of Education of Brazil (grant No. 11912/13-8), the Slovenian Research Agency (research core funding No. P1-0230), and TBU in Zlín (internal grant no. IGA/FT/2017/005, funded from the resources of specific university research). We dedicate this paper to our colleague, Professor Sandra Apers, who passed away much too early on February 5th, 2017.
utb.wos.affiliation [de Macedo, Maira Bidart; Cools, Freya; Torfs, Eveline; Cos, Paul; Cappoen, Davie] Univ Antwerp, LMPH, Fac Pharmaceut Biomed & Vet Sci, S7,Univ Pl 1, B-2610 Antwerp, Belgium; [Kimmel, Roman; Milicevic, David; Klasek, Antonin; Kafka, Stanislav] Tomas Bata Univ, Fac Technol, Vavreckova 275, CZ-76001 Zlin, Czech Republic; [Urankar, Damijana; Gazvoda, Martin; Kosmrlj, Janez] Univ Ljubljana, Fac Chem & Chem Technol, Vecna Pot 113, SI-1000 Ljubljana, Slovenia; [Peixoto, Antonio] CNRS, IPBS, UMR 5089, F-31077 Toulouse, France; [Peixoto, Antonio] Univ Toulouse, UPS, F-31000 Toulouse, France; [Verschaeve, Luc] Univ Antwerp, Dept Biomed Sci, Univ Pl 1, B-2610 Antwerp, Belgium; [Lima, Emerson Silva] Univ Fed Amazonas, Fac Pharmaceut Sci, Ave Gen Rodrigo Otavio Campos de Jordao 6200, BR-69077000 Manaus, Amazonas, Brazil; [Lycka, Antonin] Univ Hradec Kralove, Fac Sci, Rokitanskeho 62, CZ-50003 Hradec Kralove 3, Czech Republic
utb.scopus.affiliation Laboratory of Microbiology, Parasitology and Hygiene (LMPH), S7, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, Belgium; Faculty of Technology, Tomas Bata University, Vavrečkova 275, Zlín, Czech Republic; Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, Ljubljana, Slovenia; Centre National de la Recherche Scientifique, IPBS, UMR 5089, Toulouse, France; Univ. Toulouse, UPS, Toulouse, France; Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Wilrijk, Belgium; Faculty of Pharmaceutical Sciences, Federal Univeristy of Amazonas, Avenida General Rodrigo Otávio Campos de Jordão, 6200, Coroado, Manaus, Amazonas, Brazil; Faculty of Science, University of Hradec Králové, Rokitanského 62, Hradec Králové III, Czech Republic
Find Full text

Files in this item

Show simple item record