Mimicking the intramolecular hydrogen bond: Synthesis, biological evaluation, andmolecular modeling of benzoxazines and quinazolines as potential antimalarial agents

Journal of Medicinal Chemistry

Volumn 55, Issue 23, 2012, Pages 10387-10404

  Gemma, Sandra ^a,b   Camodeca, Caterina ^a,b   Brindisi, Margherita ^a,b   Brogi, Simone ^a,b   Kukreja, Gagan ^a,b   Kunjir, Sanil ^a,b   Gabellieri, Emanuele ^a,b   Lucantoni, Leonardo ^b,c   Habluetzel, Annette ^b,c   Taramelli, Donatella ^a,b,d   Basilico, Nicoletta ^a,b,d   Gualdani, Roberta ^e   Tadini Buoninsegni, Francesco ^e   Bartolommei, Gianluca ^e   Moncelli, Maria Rosa ^e   Martin, Rowena E ^f   Summers, Robert L ^f   Lamponi, Stefania ^a,b   Savini, Luisa ^a,b   Fiorini, Isabella ^a,b   Valoti, Massimo ^a   Novellino, Ettore ^a,g   Campiani, Giuseppe ^a,b   Butini, Stefania ^a,b   more..

^a UNIVERSITY OF SIENA   (Italy)

^b UNIVERSITY OF TURIN   (Italy)

^c UNIVERSITY OF CAMERINO   (Italy)

^d UNIVERSITY OF MILAN   (Italy)

^e UNIVERSITY OF FLORENCE   (Italy)

^f AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

^g UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; BENZOXAZINE DERIVATIVE; CARBENE; CHLOROQUINE; FEBRIFUGINE; N (3 BENZYL 1,2,3,4 TETRAHYDROQUINAZOLIN 7 YL) 7 CHLORO 4 AMINOQUINOLINE; N (3 PROPYL 1,2,3,4 TETRAHYDROQUINAZOLIN 7 YL) 7 CHLORO 4 AMINOQUINOLINE; QUINAZOLINE DERIVATIVE; TETRAHYDROQUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; HUMAN; HUMAN CELL; HYDROGEN BOND; MOLECULAR MODEL; MOUSE; NONHUMAN; OOCYTE; PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; XENOPUS LAEVIS;

ANIMALS; ANTIMALARIALS; BENZOXAZINES; CELL LINE; HUMANS; HYDROGEN BONDING; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MODELS, MOLECULAR; MOLECULAR MIMICRY; QUINAZOLINES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 84870986351     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300831b     Document Type: Article

References (83)

1. WHO World Malaria Report 2011; World Health Organization: Geneva, 2011; http://www.who.int/malaria/world-malaria-report-2011/en/.
2. Murray, C. J.; Rosenfeld, L. C.; Lim, S. S.; Andrews, K. G.; Foreman, K. J.; Haring, D.; Fullman, N.; Naghavi, M.; Lozano, R.; Lopez, A. D. Global malaria mortality between 1980 and 2010: a systematic analysis Lancet 2012, 379, 413-431
3. Watkins, W. M.; Sixsmith, D. G.; Spencer, H. C.; Boriga, D. A.; Kariuki, D. M.; Kipingor, T.; Koech, D. K. Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium falciparum infections in Kenya Lancet 1984, 1, 357-359
4. Olliaro, P.; Nevill, C.; LeBras, J.; Ringwald, P.; Mussano, P.; Garner, P.; Brasseur, P. Systematic review of amodiaquine treatment in uncomplicated malaria Lancet 1996, 348, 1196-1201
5. Anvikar, A. R.; Sharma, B.; Sharma, S. K.; Ghosh, S. K.; Bhatt, R. M.; Kumar, A.; Mohanty, S. S.; Pillai, C. R.; Dash, A. P.; Valecha, N. In vitro assessment of drug resistance in Plasmodium falciparum in five States of India Indian J. Med. Res. 2012, 135, 494-499
6. Neftel, K. A.; Woodtly, W.; Schmid, M.; Frick, P. G.; Fehr, J. Amodiaquine induced agranulocytosis and liver damage Br. Med. J. (Clin. Res. Ed.) 1986, 292, 721-723
7. Hatton, C. S.; Peto, T. E.; Bunch, C.; Pasvol, G.; Russell, S. J.; Singer, C. R.; Edwards, G.; Winstanley, P. Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria Lancet 1986, 1, 411-414
8. Thomas, F.; Erhart, A.; D'Alessandro, U. Can amodiaquine be used safely during pregnancy? Lancet Infect. Dis. 2004, 4, 235-239
9. Maggs, J. L.; Tingle, M. D.; Kitteringham, N. R.; Park, B. K. Drug-protein conjugates. XIV. Mechanisms of formation of protein-arylating intermediates from amodiaquine, a myelotoxin and hepatotoxin in man Biochem. Pharmacol. 1988, 37, 303-311
10. Harrison, A. C.; Kitteringham, N. R.; Clarke, J. B.; Park, B. K. The mechanism of bioactivation and antigen formation of amodiaquine in the rat Biochem. Pharmacol. 1992, 43, 1421-1430
11. Werbel, L. M.; Cook, P. D.; Elslager, E. F.; Hung, J. H.; Johnson, J. L.; Kesten, S. J.; Mcnamara, D. J.; Ortwine, D. F.; Worth, D. F. Antimalarial Drugs 0.60. Synthesis, Antimalarial Activity, and Quantitative Structure-Activity Relationships of Tebuquine and a Series of Related 5-[(7-Chloro-4-quinolinyl) amino]-3-[(alkylamino)methyl][1,1′-biphenyl]-2-ols and N -omega-Oxides1,2 J. Med. Chem. 1986, 29, 924-939
12. O'Neill, P. M.; Willock, D. J.; Hawley, S. R.; Bray, P. G.; Storr, R. C.; Ward, S. A.; Park, B. K. Synthesis, antimalarial activity, and molecular modeling of tebuquine analogues J. Med. Chem. 1997, 40, 437-448
13. O'Neill, P. M.; Harrison, A. C.; Storr, R. C.; Hawley, S. R.; Ward, S. A.; Park, B. K. The Effect of Fluorine Substitution on the Metabolism and Antimalarial Activity of Amodiaquine J. Med. Chem. 1994, 37, 1362-1370
14. Raynes, K. J.; Stocks, P. A.; O'Neill, P. M.; Park, B. K.; Ward, S. A. New 4-aminoquinoline mannich base antimalarials. 1. Effect of an alkyl substituent in the 5 ′-position of the 4 ′-hydroxyanilino side chain J. Med. Chem. 1999, 42, 2747-2751
15. Madrid, P. B.; Sherrill, J.; Liou, A. P.; Weisman, J. L.; Derisi, J. L.; Guy, R. K. Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities Bioorg. Med. Chem. Lett. 2005, 15, 1015-1018
16. Madrid, P. B.; Wilson, N. T.; DeRisi, J. L.; Guy, R. K. Parallel synthesis and antimalarial screening of a 4-aminoquinoline library J. Comb. Chem. 2004, 6, 437-442
17. Madrid, P. B.; Liou, A. P.; DeRisi, J. L.; Guy, R. K. Incorporation of an intramolecular hydrogen-bonding motif in the side chain of 4-aminoquinolines enhances activity against drug-resistant P. falciparum J. Med. Chem. 2006, 49, 4535-4543
18. Burckhalter, J. H.; Tendick, F. H. Aminoalkylphenols as antimalarials (heterocyclicamino)-alpha-amino- o -cresols; the synthesis of camoquin J. Am. Chem. Soc. 1948, 70, 1363-1373
19. O'Neill, P. M.; Ward, S. A.; Berry, N. G.; Jeyadevan, J. P.; Biagini, G. A.; Asadollaly, E.; Park, B. K.; Bray, P. G. A medicinal chemistry perspective on 4-aminoquinoline antimalarial drugs Curr. Top. Med. Chem. 2006, 6, 479-507
20. Biot, C.; Taramelli, D.; Forfar-Bares, I.; Maciejewski, L. A.; Boyce, M.; Nowogrocki, G.; Brocard, J. S.; Basilico, N.; Olliaro, P.; Egan, T. J. Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity Mol. Pharmaceutics 2005, 2, 185-193
21. O'Neill, P. M.; Mukhtar, A.; Stocks, P. A.; Randle, L. E.; Hindley, S.; Ward, S. A.; Storr, R. C.; Bickley, J. F.; O'Neil, I. A.; Maggs, J. L.; Hughes, R. H.; Winstanley, P. A.; Bray, P. G.; Park, B. K. Isoquine and related amodiaquine analogues: a new generation of improved 4-aminoquinoline antimalarials J. Med. Chem. 2003, 46, 4933-4945
22. Lawrence, R. M.; Dennis, K. C.; O'Neill, P. M.; Hahn, D. U.; Roeder, M.; Struppe, C. Development of a Scalable Synthetic Route to GSK369796 (N-tert -Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug Org. Process Res. Dev. 2008, 12, 294-297
23. O'Neill, P. M.; Park, B. K.; Shone, A. E.; Maggs, J. L.; Roberts, P.; Stocks, P. A.; Biagini, G. A.; Bray, P. G.; Gibbons, P.; Berry, N.; Winstanley, P. A.; Mukhtar, A.; Bonar-Law, R.; Hindley, S.; Bambal, R. B.; Davis, C. B.; Bates, M.; Hart, T. K.; Gresham, S. L.; Lawrence, R. M.; Brigandi, R. A.; Gomez-delas-Heras, F. M.; Gargallo, D. V.; Ward, S. A. Candidate selection and preclinical evaluation of N-tert -butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for the 21st century J. Med. Chem. 2009, 52, 1408-1415
24. Omura, Y.; Taruno, Y.; Irisa, Y.; Morimoto, M.; Saimoto, H.; Shigemasa, Y. Regioselective Mannich reaction of phenolic compounds and its application to the synthesis of new chitosan derivatives Tetrahedron Lett. 2001, 42, 7273-7275
25. Zhao, H.; Fu, H.; Qiao, R. Copper-catalyzed direct amination of ortho-functionalized haloarenes with sodium azide as the amino source J. Org. Chem. 2010, 750, 3311-3316
26. Biot, C.; Glorian, G.; Maciejewski, L. A.; Brocard, J. S. Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue J. Med. Chem. 1997, 40, 3715-3718
27. Sato, S.; Sakamoto, T.; Miyazawa, E.; Kikugawa, Y. One-pot reductive amination of aldehydes and ketones with alpha-picoline-borane in methanol, in water, and in neat conditions Tetrahedron 2004, 60, 7899-7906
28. Khurana, J. M.; Kukreja, G. Rapid reduction of nitriles to primary amines with nickel boride at ambient temperature Synth. Commun. 2002, 32, 1265-1269
29. Gemma, S.; Kunjir, S.; Coccone, S. S.; Brindisi, M.; Moretti, V.; Brogi, S.; Novellino, E.; Basilico, N.; Parapini, S.; Taramelli, D.; Campiani, G.; Butini, S. Synthesis and antiplasmodial activity of bicyclic dioxanes as simplified dihydroplakortin analogues J. Med. Chem. 2011, 54, 5949-5953
30. Summers, R. L.; Martin, R. E. Functional characteristics of the malaria parasite's chloroquine resistance transporter: implications for chemotherapy Virulence 2010, 1, 304-308
31. Martin, R. E.; Marchetti, R. V.; Cowan, A. I.; Howitt, S. M.; Broer, S.; Kirk, K. Chloroquine transport via the malaria parasite's chloroquine resistance transporter Science 2009, 325, 1680-1682
32. Martin, R. E.; Butterworth, A. S.; Gardiner, D. L.; Kirk, K.; McCarthy, J. S.; Skinner-Adams, T. S. Saquinavir inhibits the malaria parasite's chloroquine resistance transporter Antimicrob. Agents Chemother. 2012, 56, 2283-2289
33. Dive, D.; Biot, C. Ferrocene conjugates of chloroquine and other antimalarials: the development of ferroquine, a new antimalarial ChemMedChem 2008, 3, 383-391
34. P450. Site of Metabolism Prediction, version 1.1; Schrödinger, LLC: New York, 2011.
35. Maestro, version 9.2; Schrödinger, LLC: New York, 2011.
36. Gartiser, S.; Hafner, C.; Kronenberger-Schafer, K.; Happel, O.; Trautwein, C.; Kummerer, K. Approach for detecting mutagenicity of biodegraded and ozonated pharmaceuticals, metabolites and transformation products from a drinking water perspective Environ. Sci. Pollut. Res. Int. 2012, 19, 3597-3609
37. Nunes, L. G.; Gontijo, D. C.; Souza, C. J.; Fietto, L. G.; Carvalho, A. F.; Leite, J. P. The mutagenic, DNA-damaging and antioxidative properties of bark and leaf extracts from Coutarea hexandra (Jacq.) K. Schum Environ. Toxicol. Pharmacol. 2012, 33, 297-303
38. Peters, W. Drug resistance in Plasmodium berghei Vincke and Lips, 1948. I. Chloroquine resistance Exp. Parasitol. 1965, 17, 80-89
39. Bhattacharyya, D.; Sen, P. C. The effect of binding of chlorpromazine and chloroquine to ion transporting ATPases Mol. Cell. Biochem. 1999, 198, 179-185
40. Mazumder, B.; Mukherjee, S.; NagDas, S. K.; Sen, P. C. The interaction of chloroquine with transport ATPase and acetylcholine esterase in microsomal membranes of rat in vitro and in vivo Biochem. Int. 1988, 16, 35-44
41. Kongsamut, S.; Kang, J.; Chen, X. L.; Roehr, J.; Rampe, D. A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs Eur. J. Pharmacol. 2002, 450, 37-41
42. Kaplan, J. H. Biochemistry of Na,K-ATPase Annu. Rev. Biochem. 2002, 71, 511-535
43. Jones, G.; Willett, P.; Glen, R. C. Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation J. Mol. Biol. 1995, 245, 43-53
44. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 1997, 267, 727-748
45. Farid, R.; Day, T.; Friesner, R. A.; Pearlstein, R. A. New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies Bioorg. Med. Chem. 2006, 14, 3160-3173
46. Induced Fit: A novel method for fast and accurate prediction of ligand induced conformational changes in receptor active sites; Schrödinger, LLC: New York, 2006; www.schrodinger.com/productpage/14/6/75/.
47. Boukharta, L.; Keranen, H.; Stary-Weinzinger, A.; Wallin, G.; de Groot, B. L.; Aqvist, J. Computer simulations of structure-activity relationships for HERG channel blockers Biochemistry 2011, 50, 6146-6156
48. Du-Cuny, L.; Chen, L.; Zhang, S. A critical assessment of combined ligand- and structure-based approaches to HERG channel blocker modeling J. Chem. Inf. Model. 2011, 51, 2948-2960
49. Durdagi, S.; Duff, H. J.; Noskov, S. Y. Combined receptor and ligand-based approach to the universal pharmacophore model development for studies of drug blockade to the hERG1 pore domain J. Chem. Inf. Model. 2011, 51, 463-474
50. Imai, Y. N.; Ryu, S.; Oiki, S. Docking model of drug binding to the human ether-a-go-go potassium channel guided by tandem dimer mutant patch-clamp data: a synergic approach J. Med. Chem. 2009, 52, 1630-1638
51. Lees-Miller, J. P.; Subbotina, J. O.; Guo, J.; Yarov-Yarovoy, V.; Noskov, S. Y.; Duff, H. J. Interactions of H562 in the S5 helix with T618 and S621 in the pore helix are important determinants of hERG1 potassium channel structure and function Biophys. J. 2009, 96, 3600-3610
52. Masetti, M.; Cavalli, A.; Recanatini, M. Modeling the hERG potassium channel in a phospholipid bilayer: molecular dynamics and drug docking studies J. Comput. Chem. 2008, 29, 795-808
53. Mitcheson, J. S.; Chen, J.; Lin, M.; Culberson, C.; Sanguinetti, M. C. A structural basis for drug-induced long QT syndrome Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 12329-12333
54. Pearlstein, R. A.; Vaz, R. J.; Kang, J.; Chen, X. L.; Preobrazhenskaya, M.; Shchekotikhin, A. E.; Korolev, A. M.; Lysenkova, L. N.; Miroshnikova, O. V.; Hendrix, J.; Rampe, D. Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches Bioorg. Med. Chem. Lett. 2003, 13, 1829-1835
55. Recanatini, M.; Cavalli, A.; Masetti, M. Modeling HERG and its interactions with drugs: recent advances in light of current potassium channel simulations ChemMedChem 2008, 3, 523-535
56. Sintra Grilo, L.; Carrupt, P. A.; Abriel, H.; Daina, A. Block of the hERG channel by bupivacaine: electrophysiological and modeling insights towards stereochemical optimization Eur. J. Med. Chem. 2011, 46, 3486-3498
57. + channel block J. Biol. Chem. 2002, 277, 23587-23595
58. The PyMOL Molecular Graphics System, version 1.5.0.1; Schrodinger LLC: New York, 2012.
59. Desmond Molecular Dynamics System, version 3.0; D. E. Shaw Research, New York, 2011
60. Maestro-Desmond Interoperability Tools, version 3.0; Schrodinger LLC: New York, 2011.
61. Bowers, K. J.; Chow, E.; Xu, H.; Dror, R. O.; Eastwood, M. P.; Gregersen, B. A.; Klepeis, J. L.; Kolossvary, I.; Moraes, M. A.; Sacerdoti, F. D.; Salmon, J. K.; Shan, Y.; Shaw, D. E. Scalable algorithms for molecular dynamics simulations on commodity clusters. In SC '06: Proceedings of the 2006 ACM/IEEE Conference on Supercomputing, Tampa, FL, November 11-17, 2006.
62. Garg, V.; Stary-Weinzinger, A.; Sachse, F.; Sanguinetti, M. C. Molecular determinants for activation of human ether-a-go-go-related gene 1 potassium channels by 3-nitro- N -(4-phenoxyphenyl) benzamide Mol. Pharmacol. 2011, 80, 630-637
63. Trager, W.; Jensen, J. B. Human malaria parasites in continuous culture Science 1976, 193, 673-675
64. D'Elia, P.; De Matteis, F.; Dragoni, S.; Shah, A.; Sgaragli, G.; Valoti, M. DP7, a novel dihydropyridine multidrug resistance reverter, shows only weak inhibitory activity on human CYP3A enzyme(s) Eur. J. Pharmacol. 2009, 614, 7-13
65. Baranczewski, P.; Stanczak, A.; Sundberg, K.; Svensson, R.; Wallin, A.; Jansson, J.; Garberg, P.; Postlind, H. Introduction to in vitro estimation of metabolic stability and drug interactions of new chemical entities in drug discovery and development Pharmacol. Rep. 2006, 58, 453-472
66. Rossi, C.; Foletti, A.; Magnani, A.; Lamponi, S. New perspectives in cell communication: bioelectromagnetic interactions Semin. Cancer Biol. 2011, 21, 207-214
67. Jiang, M.; Dun, W.; Fan, J. S.; Tseng, G. N. Use-dependent agonist effect of azimilide on the HERG channel J. Pharmacol. Exp. Ther. 1999, 291, 1324-1336
68. +)-ATPase Methods Enzymol. 1974, 32, 277-290
69. Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. J. Protein measurement with the Folin phenol reagent J. Biol. Chem. 1951, 193, 265-275
70. Lanzetta, P. A.; Alvarez, L. J.; Reinach, P. S.; Candia, O. A. An improved assay for nanomole amounts of inorganic phosphate Anal. Biochem. 1979, 100, 95-97
71. MacroModel, version 9.9; Schrödinger, LLC, New York, 2011.
72. Jorgensen, W. L.; Maxwell, D. S.; TiradoRives, J. Development and testing of the OPLS all atom force field on conformational energetics and properties of organic liquids J. Am. Chem. Soc. 1996, 118, 11225-11236
73. Kaminski, G. A.; Friesner, R. A.; Tirado-Rives, J.; Jorgensen, W. L. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides J. Phys. Chem. B 2001, 105, 6474-6487
74. Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics J. Am. Chem. Soc. 1990, 112, 6127-6129
75. Polak, E.; Ribiere, G. Note sur la convergence de directions conjuguées Rev. Fr. Inform. Rech. Operation., 3e Année 1969, 16, 35-37
76. P450 Site of Metabolism Prediction, User Manual, version 1.1; Schrödinger Press LLC: New York, 2011.
77. Sherman, W.; Day, T.; Jacobson, M. P.; Friesner, R. A.; Farid, R. Novel procedure for modeling ligand/receptor induced fit effects J. Med. Chem. 2006, 49, 534-553
78. Schrödinger Suite 2011 Induced Fit Docking Protocol: Glide, version 5.7; Schrödinger, LLC: New York, 2011; Prime, version 3.0; Schrödinger, LLC: New York, 2011.
79. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential function for simulating liquid water J. Chem. Phys. 1983, 79, 926-935
80. Humphreys, D. D.; Friesner, R. A.; Berne, B. J. A Multiple-Time-Step Molecular-Dynamics Algorithm for Macromolecules J. Phys. Chem. 1994, 98, 6885-6892
81. Hoover, W. G. Canonical Dynamics-Equilibrium Phase-Space Distributions Phys. Rev. A 1985, 31, 1695-1697
82. Martyna, G. J.; Tobias, D. J.; Klein, M. L. Constant-Pressure Molecular-Dynamics Algorithms J. Chem. Phys. 1994, 101, 4177-4189
83. Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A Smooth Particle Mesh Ewald Method J. Chem. Phys. 1995, 103, 8577-8593