Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A

Journal of Medicinal Chemistry

Volumn 51, Issue 15, 2008, Pages 4388-4391

  Śolaja, Bogdan A ^a   Opsenica, Dejan ^b   Smith, Kirsten S ^c   Milhous, Wilbur K ^c,d   Terzić, Nataša ^a   Opsenica, Igor ^a   Burnett, James C ^e   Nuss, Jon ^f   Gussio, Rick ^g   Bavari, Sina ^b,f  

^a UNIVERSITY OF BELGRADE   (Serbia)

^b UNIVERSITY OF BELGRADE   (Serbia)

^c WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^d UNIVERSITY OF SOUTH FLORIDA   (United States)

^e SAIC FREDERICK INC   (United States)

^f UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES   (United States)

^g NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,3 PROPANEDIAMINE; AMANTADINE; BOTULINUM TOXIN A; CHLOROQUINE; METALLOPROTEINASE; N 1 (7 CHLORO 4 QUINOLINYL) 1,2 ETHANEDIAMINE; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG INHIBITION; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; IN VITRO STUDY; LIGHT CHAIN; NONHUMAN; PLASMODIUM FALCIPARUM; STRUCTURE ACTIVITY RELATION;

AMINOQUINOLINES; ANIMALS; BOTULINUM TOXIN TYPE A; CHLOROQUINE; DRUG RESISTANCE; MOLECULAR STRUCTURE; PLASMODIUM FALCIPARUM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 49449118829     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800737y     Document Type: Article

References (31)

1. Antimalarial Chemotherapy; Rosenthal, P. J., Ed.; Humana Press, Totowa, NJ, 2001, and references therein.
2. Malaria is one of three most infectious diseases, and lack of a widely available treatment regiment against the protozoan parasite Plasmodium falciparum results in 300-500 million people annually becoming ill from the disease, with over 1.5 million of these cases resulting in death. For further information, see Malaria Foundation International, http://www.malaria.org/, and the sites given therein.
3. (a) Posner, G. H.; Chang, W.; Hess, L.; Woodard, L.; Sinishtaj, S.; Usera, A. R.; Maio, W.; Rosenthal, A. S.; Kalinda, A. S.; D'Angelo, J. G.; Petersen, K. S.; Stohler, R.; Chollet, J.; Santo-Tomas, J.; Snyder, C.; Rottmann, M.; Wittlin, S.; Brun, R.; Shapiro, T. A. Malaria-Infected Mice Are Cured by Oral Administration of New Artemisinin Derivatives. J. Med. Chem. 2008, 51, 1035-1042, and references cited therein,
4. (b) Opsenica, I.; Opsenica, D.; Smith, K. S.; Milhous, W. K.; Šolaja, B. A. Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials. J. Med. Chem. 2008, 51, 2261-2266, and references cited therein,
5. (c) Vennerstrom, J. L.; Arbe-Barnes, S.; Brun, R.; Charman, S. A.; Chiu, F. C. K.; Chollet, J.; Dong, Y.; Dorn, A.; Hunziker, D.; Matile, H.; McIntosh, K.; Padmanilayam, M.; Santo Tomas, J.; Scheurer, C.; Scorneaux, B.; Tang, Y.; Urwyler, H.; Wittlin, S.; Charman, W. N. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 2004, 430, 900-904.
6. (d) Opsenica, D.; Pocsfalvi, G.; Juranić, Z.; Tinant, B.; Declercq, J.-P.; Kyle, D. E.; Milhous, W. K.; Šolaja, B. A. Cholic Acid Derivatives as 1,2,4,5-Tetraoxane Carriers: Structure and Antimalarial and Antiproliferative Activity. J. Med. Chem. 2000, 43, 3274-3282.
7. (a) Lanteri, C. A.; Johnson, J. D.; Waters, N. C. Recent Advances in Malaria Drug Discovery. Recent Pat. Anti-Infective Drug Discovery 2007, 2, 95-114.
8. (b) Egan, T. J.; Helder, M.; Marques, H.M. The role of haem in the activity of chloroquine and related antimalarial drugs. Coord. Chem. Rev. 1999, 190-192, 493-517.
9. (a) Kimberly Yearick, K.; Ekoue-Kovi, K.; Iwaniuk, D. P.; Natarajan, J. K.; Alumasa, J.; de Dios, A. C.; Roepe, P. D.; Wolf, C. Overcoming Drug Resistance to Heme-Targeted Antimalarials by Systematic Side Chain Variation of 7-Chloro-4-aminoquinolines. J. Med. Chem. 2008, 51, 1995-1998, and references cited therein,
10. (b) Miroshnikova, O. V.; Hudson, T. H.; Gerena, L.; Kyle, D. E.; Lin, A. J. Synthesis and Antimalarial Activity of New Isotebuquine Analogues. J. Med. Chem. 2007, 50, 889-896.
11. (c) Solomon, V. R.; Haq, W.; Srivastava, K.; Puri, S. K.; Katti, S. B. Synthesis and Antimalarial Activity of Side Chain Modified 4-Aminoquinoline Derivatives. J. Med. Chem. 2007, 50, 394-398.
12. (d) 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.
13. (e) Solomon, V. R.; Puri, S. K.; Srivastava, K.; Katti, S. B. Design and Synthesis of New Antimalarial Agents from 4-Aminoquinoline. Bioorg. Med. Chem. 2005, 13, 2157-2165.
14. Yeates, C. L.; Batchelor, J. F.; Capon, E. C.; Cheesman, N. J.; Fry, M.; Hudson, A. T.; Pudney, M.; Trimming, H.; Woolven, J.; Bueno, J. M.; Chicharro, J.; Fernández, E.; Fiandor, J. M.; Gargallo-Viola, D.; Gómez de las Heras, F.; Herreros, E.; León, M. L. Synthesis and Structure - Activity Relationships of 4-Pyridones as Potential Anti-malarials. J. Med. Chem. 2008, 51, 2845-2852.
15. Burgess, S. J.; Selzer, A.; Kelly, J. X.; Smilkstein, M. J.; Riscoe, M. K.; Peyton, D. H. A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum. J. Med. Chem. 2006, 49, 5623-5625.
16. (a) Biot, C.; Daher, W.; Ndiaye, C. M.; Melnyk, P.; Pradines, B.; Chavain, N.; Pellet, A.; Fraisse, L.; Pelinski, L.; Jarry, C.; Brocard, J.; Khalife, J.; Forfar-Bares, I.; Dive, D. Probing the Role of the Covalent Linkage of Ferrocene into a Chloroquine Template. J. Med. Chem. 2006, 49, 4707-4714.
17. (b) Biot, C.; Glorian, G.; Lucien, A.; Maciejewski, L. A.; Brocard, J. Synthesis and Antimalarial Activity in Vitro and in Vivo of a New Ferrocene-Chloroquine Analogue. J. Med. Chem. 1997, 40, 3715-3718.
18. (a) 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-chloroquinolin-4-yl)heteroalkanediamines. J. Med. Chem. 1998, 41, 4360-4364.
19. (b) Vennerstrom, J. L.; Ellis, W. Y.; Ager, A. L.; Dorn, A.; Andersen, S. L.; Gerena, L.; Milhous, W. K. Bisquinolines. 1. N,N-Bis(7- chloroquinolin-4-yl)alkanediamines with potential against Chloroquine-Resistant Malaria. J. Med. Chem. 1992, 35, 2129-2134.
20. (a) Fawaz Mzayek, F.; Deng, H.; Mather, F. J.; Wasilevich, E.; Huayin Liu, H.; Hadi, C. M.; Chansolme, D. H.; Murphy, H. A.; Melek, B. H.; Tenaglia, A. N.; Mushatt, D. M.; Dreisbach, A. W.; Lertora, J. J. L.; Krogstad, D. J. Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers. PLoS Clin. Trials 2007, 2, e6.
21. (b) De, D.; Krogstad, F. M.; Byers, L. D.; Krogstad, D. J. Structure - Activity Relationships for Antiplasmodial Activity among 7-Substituted 4-Aminoquinolines. J. Med. Chem. 1998, 41, 4918-4926, and references cited therein.
22. Burnett, J. C.; Schmidt, J. J.; Stafford, R. G.; Panchal, R. G.; Nguyen, T. L.; Hermone, A. R.; Vennerstrom, J. L.; McGrath, C. F.; Lane, D. J.; Sausville, E. A.; Zaharevitz, D. W.; Gussio, R.; Bavari, S. Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity. Biochem. Biophys. Res. Commun. 2003, 310 (1), 84-93.
23. Burnett, J. C.; Opsenica, D.; Sriraghavan, K.; Panchal, R. K.; Ruthel, G.; Hermone, A. R.; Nguyen, T. L.; Kenny, T. A.; Lane, D. J.; McGrath, C. F.; Schmidt, J. J.; Vennerstrom, J. L.; Gussio, R.; Bogdan, A.; Šolaja, B. A.; Bavari, S. A Refined Pharmacophore Identifies Potent 4-Amino-7- chloroquinoline-Based Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease. J. Med. Chem. 2007, 50, 2127-2136.
24. Burnett, J. C.; Henchal, E. A.; Schmaljohn, A. L.; Bavari, S. The evolving field of biodefence: therapeutic developments and diagnostics. Nat. Rev. Drug Discovery 2005, 4, 281-297.
25. For further elaboration of the chirality issues see ref 10 and Foye's Principles of Medicinal Chemistry, 5th ed.; Williams, D. A., Lemke, T. L. , Eds.; Lippincott Williams & Wilkins: Chicago, 2002, p 49.
26. All synthesized compounds were screened in vitro against three P. falciparum strains: D6 (CQ and MFQ susceptible strain D6 (clone of Sierra I/UNC isolate)), W2 (chloroquine-resistant, susceptible to mefloquine, (clone of Indochina I isolate)), and TM91C235 (Thailand), a multidrug-resistant strain (clone of South-East Asian isolate) following the protocol given in ref 3c.
27. To the best of our knowledge, the selectivity index < 1 involving an 3-chloro-4-aminoquinoline and W2 clone was found only on few occasions: bis(aminoquinolines) (ref 7), ferroquine (ref 6b), and AQ-40 (ref 8b).
28. (a) Schmidt, J. J.; Stafford, R. G. A high-affinity competitive inhibitor of type A botulinum neurotoxin protease activity. FEBS Lett. 2002, 532, 423-426.
29. (b) Schmidt, J. J.; Bostian, K. A. Proteolysis of synthetic peptides by type A botulinum neurotoxin. J. Protein Chem. 1995, 14, 703-708.
30. (c) Schmidt, J. J.; Bostian, K. A. Endoproteinase activity of type A botulinum neurotoxin: substrate requirements and activation by serum albumin. J. Protein Chem. 1997, 16, 19-26.
31. (d) Schmidt, J. J.; Stafford, R. G.; Bostian, K. A. Type A botulinum neurotoxin proteolytic activity: development of competitive inhibitors and implications for substrate specificity at the S1¢ binding subsite. FEBS Lett. 1998, 435, 61-64.