Synthesis, Antimalarial Activity, and Molecular Modeling of New Pyrrolo[1,2-a]quinoxalines, Bispyrrolo[1,2-a]quinoxalines, Bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and Bispyrrolo[1,2-a]thieno[3,2-e]pyrazines

Journal of Medicinal Chemistry

Volumn 47, Issue 8, 2004, Pages 1997-2009

  Guillon, Jean ^a   Grellier, Philippe ^b   Labaied, Mehdi ^b   Sonnet, Pascal ^c   Léger, Jean Michel ^a   Déprez Poulain, Rébecca ^d   Forfar Bares, Isabelle ^a   Dallemagne, Patrick ^e   Lemaître, Nicolas ^a   Péhourcq, Fabienne ^f   Rochette, Jacques ^c   Sergheraert, Christian ^d   Jarry, Christian ^a  

^a Laboratoire de Pharmacochimie   (France)

^b MUSÉUM NATIONAL D'HISTOIRE NATURELLE   (France)

^c UNIVERSITÉ DE PICARDIE JULES VERNE   (France)

^d INSTITUT PASTEUR DE LILLE   (France)

^e CENTRE D ETUDES ET DE RECHERCHE SUR LE MÉDICAMENT DE NORMANDIE   (France)

^f UNIVERSITÉ DE BORDEAUX   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BISPYRIDO[3,2 E]PYRROLO[1,2 A]PYRAZINE; BISPYRROLO[1,2 A]QUINOXALINE; BISPYRROLO[1,2 A]THIENO[3,2 E]PYRAZINE; CHLOROQUINE; HEMATIN; PYRAZINE DERIVATIVE; PYRROLO[1,2 A]QUINOXALINE; QUINOXALINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOTOXICITY; DRUG RESISTANCE; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; MOLECULAR MODEL; NONHUMAN; PARTITION COEFFICIENT; PLASMODIUM FALCIPARUM; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIMALARIALS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DRUG RESISTANCE; ERYTHROCYTES; HEMEPROTEINS; HUMANS; MODELS, MOLECULAR; PLASMODIUM FALCIPARUM; PROTEIN BINDING; PYRAZINES; PYRIDINES; PYRROLES; QUINOXALINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 11144354006     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0310840     Document Type: Article

References (63)

1. Mishra, S. K.; Satpathy, S. K.; Mohanty, S. Survey of Malaria Treatment and Deaths. Bull. W. H. O. 1999, 77, 1020.
2. Bouland, P. B. Drug Resistance in Malaria; World Health Organization: Geneva, Switzerland, 2001.
3. Ridley, R. G. Medicinal need, scientific opportunity and the drive for antimalarial drugs. Nature 2002, 415, 686-693.
4. Ursos, L. M. B.; Roepe, P. D. Chloroquine Resistance in the Malaria Parasite, Plasmodium falciparum. Med. Res. Rev. 2002, 22, 465-491.
5. White, N. J. Antimalarial Drug Resistance: The Pace Quickens. J. Antimicrob. Chemother. 1992, 30, 571-585.
6. Surrey, A. R.; Hammer, H. F. Some 7-substituted 4-aminoquinoline derivatives. J. Am. Chem. Soc. 1946, 68, 113-116.
7. Van Est, H. G.; Skamene, G. E.; Schurr, E. Chemotherapy of malaria: a battle against the odds? Clin. Invest. Med. 1993, 16, 285-293.
8. Dorn, A.; Stoffel, R.; Matile, H.; Bubendorf, A.; Ridley, R. G. Malrial Haemozoin/Beta-Haematin Supports Haem Polimerization in the Absence of Protein. Nature 1995, 374, 269-271.
9. Dorn, A.; Vippagunta, S. R.; Matile, H.; Jaquet, C.; Vennerstrom, J. L.; Ridley, R. G. An Assessment of Drug-Haematin Binding as Mechanism for Inhibition of Haematin Polimerization by Quinoline Antimalarials. Biochem. Pharmacol. 1998, 55, 727-736.
10. Ginsburg, H.; Fatim, O.; Zhang, J.; Krugliak, M. Inhibition of Glutathione-Dependent Degradation of Heme by Chloroquine and Amodiaquine as a Possible Basis for Their Antimalarial Mode of Action. Biochem. Pharmacol. 1998, 56, 1305-1313.
11. Krogstad, D. J.; Gluzman, I. Y.; Kyle, D. E.; Oduola, A. M.; Martin, S. K.; Milhous, W. K.; Schlesinger, P. H. Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance. Science 1987, 238, 1283-1285.
12. Ginsburg, H.; Stein, W. D. Kinetic modeling of chloroquine uptake by malaria-infected erythrocytes. Biochem. Pharmacol. 1991, 41, 1463-1470.
13. + exchanger determines chloroquine uptake in Plasmodium falciparum. J. Cell Biol. 1998, 140, 335-345.
14. Bray, P. G.; Janneh, O.; Raynes, K. J.; Mungthin, M.; Ginsburg, H.; Ward, S. A. Cellular uptake of chloroquine is dependent on binding to ferriprotoporphyrin IX and is dependent on NHE activity in Plasmodium falciparum. J. Cell Biol. 1999, 145, 363-376.
15. Reed, M. B.; Saliba, K. J.; Caruana, S. R.; Kirk, K.; Cowman, A. F. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 2000, 403, 906-909.
16. Vennerstrom, J. L.; Ellis, W. Y.; Ager, A. L.; Andersen, S. L.; Gerena, L.; Milhous, W. K. Bisquinolines. N,N-Bis(7-chloroquinolin-4-yl)alkanediamines with Potential against Chloroquine-Resistant Malaria. J. Med. Chem. 1992, 35, 2129-2134.
17. Ridley, R. G.; Matile, H.; Jaquet, C.; Dorn, A.; Hofheinz, W.; Leupin, W.; Masciadri, R.; Theil, F.-P.; Richter, W. F.; Girometta, M.-A.; Guenzi, A.; Urwyler, H.; Gocke, E.; Potthast, J.-M.; Csato, M.; Thomas, A.; Peters, W. Antimalarial Activity of the Bisquinoline trans-N1,N2-Bis(7-chloroquinolin4-yl)cyclohexane-1,2 diamine: Comparison of Two Stereoisomers and Detailed Evaluation of the S,S Enantiomer, Ro 47-7737. J. Antimicrob. Chemother. 1997, 41, 677-686.
18. Kalidas, P.; DeWitt Blanton, C. Synthesis of 1,4-Bis(6-methoxy-8-quinolylaminoalkyl)piperazines as potential prophylactic antimalarial agents. J. Med. Chem. 1973, 16, 1391-1394.
19. Shetty, R. V.; Dewitt Blanton, C. Synthesis and Antiprotozoan Activity of N,N′-Disubstituted Piperazines. Eur. J. Med. Chem. 1979, 14, 353-356.
20. Raynes, K.; Galatis, D.; Cowman, A. F.; Tilley, L.; Deady, L. W. Synthesis and Activity of Some Antimalarial Bisquinolines. J. Med. Chem. 1995, 38, 204-206.
21. Raynes, K.; Foley, M.; Tilley, L.; Deady L. W. Novel Bisquinoline Antimalarials. Biochem. Pharmacol. 1996, 52, 551-559.
22. Vennerstrom, J. L.; Ager, A. L.; Dorn, A.; Andersen, S. L.; Gerena, L.; Ridley, R. G.; Milhous, W. K. Bisquinolines. 2. Antimalarial N,N-Bis(7-chloroquinolin4-yl)heteroalkanedamines. J. Med. Chem. 1998, 41, 4360-4364.
23. Raynes, K. Bisquinoline Antimalarials: Their Role in Malaria Chemotherapy. Int. J. Parasitol. 1999, 29, 367-379.
24. Walls, L. P. Researches in the Phenanthridine Series. J. Chem. Soc. 1935, 1405-1410.
25. Girault, S.; Grellier, P.; Berecibar, A.; Maes, L.; Mouray, E.; Lemière, P.; Debreu, M. A.; Davioud-Charvet, E.; Sergheraert, C. Antimalarial, Antitrypanosomal, and Antileishmanial Activities and Cytotoxicity of Bis(9-amino-6-ch[oro-2-methoxyacridines): influence of the linker. J. Med. Chem. 2000, 43, 2646-2654.
26. Girault, S.; Delarue, S.; Grellier, P.; Berecibar, A.; Maes, L.; Quirijnen, L.; Lemière, P.; Debreu-Fontaine, M. A.; Sergheraert, C. Antimalarial in-vivo Activity of Bis(9-amino-6-chloro-2-methoxyacridines). J. Pharm. Pharmacol. 2001, 53, 935-938.
27. Guillon, J.; Dumoulin, H.; Dallemagne, P.; Reynolds, R.; Rault, S. Synthesis and Antituberculosis Activity of New Phenylpyrrolo-[1,2-a]quinoxalinylpyrrole Carboxylic Acid Derivatives. Pharm. Pharmacol. Commun. 1998, 4, 33-38.
28. Guillon, J.; Dallemagne, P.; Pfeiffer, B.; Renard, P.; Manechez, D.; Kervran, A.; Rault, S. Synthesis of New Pyrrolo[1,2-a]-quinoxalines: Potential Non-Peptide Glucagon Receptor Antagonists. Eur. J. Med. Chem. 1998, 33, 293-308.
29. Guillon, J.; Boulouard, M.; Lisowski, V.; Stiebing, S.; Lelong, V.; Dallemagne, P.; Rault, S. Synthesis of New 2-(Aminomethyl)-4-phenylpyrrolo[1,2-a]quinoxalines and Their Preliminary In-Vivo Central Dopamine Antagonist Activity Evaluation in Mice. J. Pharm. Pharmacol. 2000, 52, 1369-1375.
30. 3 Receptors. Synthesis and Biological Evaluation of Piperazinopyridopyrrolopyrazines, Piperazinopyrroloquinoxalines, and Piperazinopyridopyrroloquinoxaline. J. Med. Chem. 1997, 40, 1808-1819.
31. Kauffman, J. M.; Litak, P. T.; Boyko, W. J. Syntheses and Photophysical Properties of Fluorescent Dibenzofurans, a Dibenzothiophene, and Carbazoles Substituted with Benzoxazole and Hydroxyl Groups To Produce Excited State Intramotecular Proton-Transfer. J. Heterocycl. Chem. 1995, 32, 1541-1555.
32. Zhang, Z.; Tillekeratne, L. M. V.; Hudson, R. A. Synthesis of Isomeric Analogues of Coenzyme Pyrroloquinoline Quinone (PQQ). Synthesis 1996, 3, 377-382.
33. Nagarajan, K.; Ranga Rao, V.; Venkateswarlu, A. Condensed Heterotricycles: Pyrrolo[1,2-a]quinoxaline Derivatives. Indian J. Chem. 1972, 10, 344-350.
34. 3 Receptors. Synthesis and Biological Evaluation of Piperazinopyrrolothienopyrazines. J. Med. Chem. 1996, 39, 2068-2080.
35. Egan, T. J.; Marques, H. M. The Role of Haem in the Activity of Chloroquine and Related Antimalarial Drugs. Coord. Chem. Rev. 1999, 190-192, 493-517.
36. Hawley, S. R.; Bray, P. G.; Mungthin, M.; Atkinson, J. D.; O'Neill, P. M.; Ward, S. A. Relationship between Antimalarial Drug Activity, Accumulation, and Inhibition of Heme Polymerization in Plasmodium falciparum In Vitro. Antimicrob. Agents Chemother. 1998, 42, 682-686.
37. Buller, R.; Peterson, M. L.; Almarsson, Ö.; Leiserowitz, L. Quinoline Binding Site on Malaria Pigment Crystal: A Rational Pathway for Antimalaria Drug Design. Cryst. Growth Des. 2002, 2, 553-562.
38. Sullivan, D. J. Theories on Malarial Pigment Formation and Quinoline Action. Int. J. Parasitol. 2002, 32, 1645-1653.
39. Slater, A. F. G.; Cerami, A. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature 1992, 355, 167-169.
40. Sullivan, D. J.; Matile, H.; Ridley, R. G.; Goldberg, D. E. A common mechanism for blockade of heme polymerization by antimalarial quinolines. J. Biol. Chem. 1998, 273, 31103-31107.
41. Raynes, K.; Foley, M.; Tilley, L.; Deady, L. W. Novel Bisquinoline Antimalarials. Biochem. Pharmacol. 1996, 52, 551-559.
42. Fitch, C. D.; Cai, G.; Chen, Y.-F.; Shoemaker, J. D. Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria. Biochim. Biophys. Acta 1999, 1454, 31-37.
43. Ayad, F.; Tilley, L.; Deady, L.-W. Synthesis, Antimalarial Activity and Inhibition of Haem Detoxification of Novel Bisquinolines. Bioorg. Med. Chem. Lett. 2001, 11, 2075-2077.
44. Ferrari, V.; Cutler, D. Temperature Dependence of the Acid Dissociation Constants of Chloroquine. J. Pharm. Sci. 1987, 76, 554-557.
45. Pehourcq, F.; Thomas, J.; Jarry, C. A microscale HPLC method for the evaluation of octanol-water partition coefficients in a series of new 2-amino-2-oxazolines. J. Liq. Chromatogr. Relat. Technol. 2000, 23, 443-453.
46. a were calculated using ACD/pKa dB software from Avanced Chemistry Development Inc., Toronto, Canada. Hawley, S.; Bray, P. C.; O'Neill, P. M.; Park, B. K.; Ward, S. A. The role of drug accumulation in 4-aminoquinoline antimalarial potency. The influence of structural substitution and physicochemical properties. Biochem. Pharmacol. 1996, 52, 723-733.
47. Pagola, S.; Stephens, P. W.; Scott Bohle, D.; Kosar, A. D.; Madsen, S. K. The Structure of Malaria Pigment β-Haematin. Nature 2000, 404, 307-310.
48. Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as Supplementary Publication Nos. CCDC-172281 and CCDC-177407. Copies of the data can be obtained free of charge on application to CCDC, University Chemical Lab, 12 Union Road, Cambridge, CB2 1EZ, U.K. (fax, international code + 44-1223/336-033; e-mail, deposit@ccdc.cam.ac.uk).
49. Stewart, J.; Mopac, J. P. A Semiempirical Molecular-Orbital Program. J. Comput.-Aided Mol. Des. 1990, 4, 1-45.
50. Discover; Biosym Technologies Inc.: San Diego, CA, 1993.
51. Hariharan, P. C.; Pople, J. A. Influence of polarization functions on MO hydrogenation energies. Theor. Chim. Acta 1973, 28, 213-222.
52. Moreau, S.; Perly, B.; Biguet, J. Interaction of chloroquine with ferriprotophorphyrin IX. Nuclear magnetic resonance study. Biochimie 1982, 64, 1015-1025.
53. Pandey, A. V.; Bisht, H.; Babbarwal, V. K.; Srivastav, J.; Pandey, K. C. ; Chauhan, V. S. Mechanism of Malaria Haem Detoxification Inhibition by Chloroquine. Biochem. J. 2001, 355, 333-338.
54. North, A. C. T.; Phillips, D. C.; Mathews, F. S. A Semi-empirical Method of Absorption Correction. Acta Crystallogr. 1968, A24, 351-359.
55. Sheldrick, G. M.; Kröger, C.; Goddard, R. SHELX 86 in Crystallographic Computing 3; Oxford University Press: New York, 1985; pp 175-189.
56. Sheldrick, G. M. SHELX 93, Program for the Refinement of the Crystal Structures; University of Göttingen: Göttingen Germany, 1993.
57. 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.
58. Stocks, P. A.; Raynes, K. J.; Bray, P. G.; Park, B. K.; O'Neill, P. M.; Ward, S. A. Novel Short Chain Chloroquine Analogues Retain Activity against Chloroquine Resistant K1 Plasmodium falciparum. J. Med. Chem. 2002, 45, 4975-4983.
59. Schmidt, M. W.; Baldridge, K. K.; Boatz, J. A.; Elbert, S. T.; Gordon, M. S.; Jensen, J. H.; Koseki, S.; Matsunaga, N.; Nguyen, K.; Su, S.; Windus, T. L.; Dupuis, M.; Montgomery, J. A. General Atomic and Molecular Electronic Structure System. J. Comput. Chem. 1993, 14, 1347-1363.
60. Trager, W.; Jensen, J. B. Human Malarial Parasites in Continuous Culture. Science 1976, 193, 673-677.
61. Desjardins, R. E.; Canfield, C. J.; Haynes, J. D.; Chulay, J. D. Quantitative Assessment of Antimalarial Activity in vitro by a Semiautomated Microdilution Technique. Antimicrob. Agents Chemother. 1979, 16, 710-718.
62. Chou, A. C.; Fitch, C. D. Control of Heme Polymerase by Chloroquine and Other Quinoline Derivatives. Biochem. Biophys. Res. Commun. 1993, 195, 422-428.
63. Asakura, T.; Minakata, K.; Adachi, K.; Russel, M. O.; Schwartz, E. Denatured Hemoglobin in Sickle Erythrocytes. J. Clin. Invest. 1977, 59, 633-640.