2,4-Dialkyl-8,9,10,11-tetrahydrobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7, 12(2H,4H)-tetraones as new leads against Mycobacterium tuberculosis

European Journal of Medicinal Chemistry

Volumn 77, Issue , 2014, Pages 409-421

  Claes, Pieter ^a   Cappoen, Davie ^b   Uythethofken, Cynthia ^a   Jacobs, Jan ^a   Mertens, Birgit ^c   Mathys, Vanessa ^b   Verschaeve, Luc ^c,d   Huygen, Kris ^b   De Kimpe, Norbert ^a  

^a GHENT UNIVERSITY   (Belgium)

^b OD Communicable and Infectious Diseases   (Belgium)

^c SCIENTIFIC INSTITUTE OF PUBLIC HEALTH   (Belgium)

^d UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Acute toxicity; Benzo g pyrimido 4,5 c isoquinolinetetraones; Genotoxicity; MDR M.tb; Mycobacterium tuberculosis; Tuberculosis

Indexed keywords

2,4 DI HEPTYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI HEXYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI ISO BUTYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI ISO BUTYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI ISO PENTYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI ISO PENTYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI ISO PROPYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI ISO PROPYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N BUTYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N BUTYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N HEPTYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N HEXYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N PENTYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N PENTYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N PROPYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DI N PROPYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DIETHYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DIMETHYL 8,9,10,11 TETRAHYDRO 8,11 ETHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 2,4 DIMETHYL 8,9,10,11 TETRAHYDRO 8,11 METHANOBENZO[G]PYRIMIDO[4,5 C]ISOQUINOLINE 1,3,7,12 (2H,4H)TETRAONE; 5,8 DIHYDROXY 1,2,3,4 TETRAHYDRO 1,4 ETHANONAPHTHALENE 6 CARBOXALDEHYDE; 5,8 DIHYDROXY 1,2,3,4 TETRAHYDRO 1,4 METHANONAPHTHALENE 6 CARBOXALDEHYDE; 5,8 DIMETHOXY 1,2,3,4 TETRAHYDRO 1,4 ETHANONAPHTHALENE 6 CARBOXALDEHYDE; 5,8 DIMETHOXY 1,2,3,4 TETRAHYDRO 1,4 METHANONAPHTHALENE 6 CARBOXALDEHYDE; 6 AMINO 1,3 DI ISO PENTYLURACIL; 6 AMINO 1,3 DI N HEPTYLURACIL; 6 AMINO 1,3 DI N PENTYLURACIL; 6 AMINO 1,3 DIMETHYLURACIL; 6 AMINOURACIL; ISOQUINOLINE DERIVATIVE; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; PYRIMIDINONE DERIVATIVE; QUINONE DERIVATIVE;

ANTIMICROBIAL ACTIVITY; ARTICLE; COMET ASSAY; DRUG SYNTHESIS; MACROPHAGE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; ANIMAL; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; GROWTH, DEVELOPMENT AND AGING; MICROBIAL SENSITIVITY TEST; MOUSE; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUBERCULOSIS, MULTIDRUG-RESISTANT;

ANIMALS; ANTITUBERCULAR AGENTS; CELL LINE; DOSE-RESPONSE RELATIONSHIP, DRUG; ISOQUINOLINES; MACROPHAGES; MICE; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; MYCOBACTERIUM TUBERCULOSIS; PYRIMIDINONES; QUINONES; STRUCTURE-ACTIVITY RELATIONSHIP; TUBERCULOSIS, MULTIDRUG-RESISTANT;

EID: 84897446773     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.03.024     Document Type: Article

References (21)

1. WHO. http://www.who.int/tb/publications/global-report/en/, 2012.
2. A. Koul, E. Arnoult, N. Lounis, J. Guillemont, and K. Andries The challenge of new drug discovery for tuberculosis Nature 469 2011 483 490
3. D. Cappoen, J. Jacobs, T. Nguyen Van, S. Claessens, G. Diels, R. Anthonissen, R. Einarsdottir, T.M. Fauville, L. Verschaeve, K. Huygen, and N. De Kimpe European Journal of Medicinal Chemistry 48 2012 57 68
4. H. Holland, and P. Viski A short synthesis of two chiral anthracycline AB synthons Journal of Organic Chemistry 56 1991 5226 5229
5. R.L. Nyland II, M. Luo, M.R. Kelley, and R.F. Borch Design and synthesis of novel quinone inhibitors targeted to the redox function of apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (Ape1/Ref-1) Journal of Medicinal Chemistry 53 2010 1200 1210
6. H. Du, B. Zhao, and Y. Shi Cu (I)-catalyzed diamination of conjugated olefins with tunable anionic counterions. A possible approach to asymmetric deamination Organic Syntheses 86 2009 315 324
7. R. Matsievitch, D. Tworowski, Heterocyclic Compounds and Uses Thereof in the Treatment of Sexual Disorders PCT Int. Appl., 2007110868, 04 Oct 2007.
8. J.A. Valderrama, R. Araya-Maturana, F. Gonzáles, R. Tapia, F. Fariña, and M.C. Paredes Studies on quinones. Part 21. Regioselective synthesis of tetracyclic quinones related to rabelomycin Journal of the Chemical Society, Perkin Transactions 1 1991 555 559
9. J.A. Valderrama, M. Florencia, P. Colonelli, Pamela, and D. Vásquez Studies on quinones. Part 41: synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones Bioorganic & Medicinal Chemistry 17 2006 2777 2780
10. J.A. Valderrama, P. Colonelli, D. Vásquez, M. Florencia González, J.A. Rodríguez, and C. Theoduloz Studies on quinones. Part 44: novel angucyclinone N-heterocyclic analogues endowed with antitumoral activity Bioorganic & Medicinal Chemistry 16 2008 10172 10181
11. J. Iribarra, D. Vásquez, C. Theoduloz, J. Benites, D. Ríos, and J. Valderrama Synthesis and antitumor evaluation of 6-aryl-substituted benzo[j]phenanthridine-and benzo[g]pyrimido [4, 5-c] isoquinolinequinones Molecules 17 2012 11616 11629
12. D. Pralay, S. Dharminder, S. Bikram, Substituted Cyclohexane-1, 3-dione Compounds, Process for Preparation Thereof and its Applications Appl., 2011117881, 29 Sep 2011.
13. D. Forge, D. Cappoen, D. Stanicki, T. Huang, L. Verschaeve, K. Huygen, and J.J. Vanden Eynde 1,4-diarylpiperazines and analogs as anti-tubercular agents: synthesis and biological evaluation European Journal of Medicinal Chemistry 49 2012 95 101
14. D. Cappoen, D. Forge, F. Vercammen, V. Mathys, M. Kiass, V. Roupie, R. Anthonissen, L. Verschaeve, J.J. Vanden Eynde, and K. Huygen Biological evaluation of bisbenzaldehydes against four Mycobacterium species European Journal of Medicinal Chemistry 63 2013 231 738
15. P. Claes, D. Cappoen, B. Mbala, J. Jacobs, B. Mertens, V. Mathys, L. Verschaeve, K. Huygen, and N. De Kimpe Synthesis and antimycobacterial activity of analogues of the bioactive natural products sampangine and cleistopholine European Journal of Medicinal Chemistry 67C 2013 98 110
16. G. Repetto, A. del Peso, and J.L. Zurita Neutral red uptake assay for the estimation of cell viability/cytotoxicity Nature Protocols 3 2008 1125 1131
17. B.A. Hanna, A. Ebrahimzadeh, B.L. Elliot, M.A. Morgan, S.M. Novak, and A.M. Vannier Multicenter evaluation of the BACTEC MGIT 960 system for recovery of mycobacteria Journal of Clinical Microbiology 37 1999 748 752
18. R.R. Tice, E. Agurell, D. Anderson, B. Burlinson, A. Hartmann, H. Kobayashi, Y. Miyamae, E. Rojas, J.C. Ryu, and Y.F. Sasaki Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing Environmental and Molecular Mutagenesis 35 2000 206 211
19. L. Verschaeve, J. Van Gompel, L. Thilemans, L. Regniers, P. Vanparys, and D. Van der Lelie Environmental and Molecular Mutagenesis 33 1999 240 248
20. W.M. Westerink, J.C. Stevenson, A. Lauwers, G. Griffioen, G.J. Horbach, and W.G. Schoonen Mutation Research 676 2009 113 130
21. M. Fenton, and M. Vermeulen Immunopathology of tuberculosis: roles of macrophages and monocytes Infection and Immunity 64 1996 683 690