Activity of and initial mechanistic studies on a novel antileishmanial agent identified through in silico pharmacophore development and database searching

Journal of Medicinal Chemistry

Volumn 49, Issue 14, 2006, Pages 4196-4207

  Delfín, Dawn A ^a   Bhattacharjee, Apurba K ^b   Yakovich, Adam J ^a   Werbovetz, Karl A ^a  

^a OHIO STATE UNIVERSITY   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; ANTILEISHMANIAL AGENT; BTB 06237; BTB 06256; MILTEFOSINE; UNCLASSIFIED DRUG;

AMASTIGOTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG STRUCTURE; FLUORESCENCE MICROSCOPY; IC 50; LEISHMANIA DONOVANI; LEISHMANIA MEXICANA; MEMBRANE POTENTIAL; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; PHARMACOPHORE; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

ANILINE COMPOUNDS; ANIMALS; CELL LINE; LEISHMANIA; LEISHMANIA DONOVANI; LEISHMANIA MEXICANA; MACROPHAGES; MEMBRANE POTENTIALS; MICE; MICROSCOPY, ELECTRON, TRANSMISSION; MICROSCOPY, FLUORESCENCE; MITOCHONDRIA; MODELS, MOLECULAR; NITRO COMPOUNDS; NITROBENZENES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFIDES; SULFONAMIDES; TRYPANOCIDAL AGENTS;

EID: 33745825571     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060156v     Document Type: Article

References (35)

1. Leishmaniasis: Burden of Disease, http://www.who.int/leishmaniasis (posting date Dec 29, 2005).
2. Magill, A. J. Leishmaniasis. In Tropical Medicine and Emerging Infectious Diseases, 8th ed.; Strickland, G. T., Ed.; W. B. Saunders Co.: Philadelphia, PA, 2000; pp 665-687.
3. Leishmaniasis: Disease Information. http://www.who.int/tdr/diseases/ leishmaniasis (posting date Dec 29, 2005).
4. Singh, S.; Sivakumar, R. Challenges and New Discoveries in the Treatment of Leishmaniasis. J. Infect. Chemother. 2004, 10, 307-315.
5. Davis, A. J.; Kedzierski, L. Recent Advances in Antileishmanial Drug Development. Curr. Opin. Invest. Drugs 2005, 6, 163-169.
6. Ouellette, M.; Drummelsmith, J.; Papadopoulou, B. Leishmaniasis: Drugs in the Clinic, Resistance and New Developments. Drug Resist. Updates 2004, 7, 257-266.
7. Croft, S. L.; Barrett, M.; Urbina, J. Chemotherapy of Trypanosomiases and Leishmaniasis. Trends Parasitol. 2005, 21, 508-512.
8. Bhattacharya, G.; Salem, M. M.; Werbovetz, K. A. Antileishmanial Dinitroaniline Sulfonamides with Activity Against Parasite Tubulin. Bioorg. Med. Chem. Lett. 2002, 12, 2395-2398.
9. Werbovetz, K. A.; Sackett, D. L.; Delfin, D.; Bhattacharya, G.; Salem, M.; Obrzut, T.; Rattendi, D.; Bacchi, C. Selective Antimicrotubule Activity of N1-Phenyl-3,5-dinitro-N4,N4-di-n-propylsulfonilamide (GB-II-5) against Kinetoplastid Parasites. Mol. Pharmacol. 2003, 64, 1325-1333.
10. 4-Substituted 3,5-Dinitroaniline Sulfanilamides against African Trypanosomes and Leishmania. J. Med. Chem. 2004, 47, 1823-1832.
11. Paulin, J. J. Conformation of a Single Mitochondrion in the Trypomastigote Stage of Trypanosoma cruzi. J. Parasitol. 1983, 69, 242-244.
12. Simpson, L.; Kretzer, F. The Mitochondrion in Dividing Leishmania tarentolae Cells is Symmetric and Circular and Becomes a Single Asymmetric Tubule in Non-Dividing Cells Due to Division of the Kinetoplast Portion. Mol. Biochem. Parasitol. 1997, 87, 71-78.
13. Docampo, R.; De Souza, W.; Miranda, K.; Rohloff, P.; Moreno, S. N. J. Acidocalcisomes-Conserved from Bacteria to Man. Nat. Rev.-Microbiol. 2005, 3, 251-261.
14. Arnoult, D.; Akarid, K.; Grodet, A.; Petit, P. X.; Estaquier, J.; Ameisen, J. C. On the Evolution of Programmed Cell Death: Apoptosis of the Unicellular Eukaryote Leishmania major Involves Cysteine Proteinase Activation and Mitochondrion Permeabilization. Cell Death Differ. 2002, 9, 65-81.
15. Zangger, H.; Mottram, J. C.; Fasel, N. Cell Death in Leishmania Induced by Stress and Differentiation: Programmed Cell Death or Necrosis. Cell Death Differ. 2002, 9, 1126-1139.
16. Lee, N.; Bertholet, S.; Debrabant, A.; Muller, J.; Duncan, R.; Nakhasi, H. L. Programmed Cell Death in the Unicellular Protozoan Parasite Leishmania. Cell Death Differ. 2002, 9, 53-64.
17. Bhattacharjee, A. K.; Geyer, J. A.; Woodard, C. L.; Kathcart, A. K.; Nichols, D. A.; Prigge, S. T.; Li, Z.; Mott, B. T.; Waters, N. C. A Three-Dimensional in Silico Pharmacophore Model for Inhibition of Plasmodium falciparum Cyclin-Dependent Kinases and Discovery of Different Classes of Novel Pfmrk Specific Inhibitors. J. Med. Chem. 2004, 47, 5418-5426.
18. Desai, P. V.; Patny, A.; Sabnis, Y.; Tekwani, B.; Gut, J.; Rosenthal, P.; Srivastava, A.; Avery, M. Identification of Novel Parasitic Cysteine Protease Inhibitors Using Virtual Screening. 1. The ChemBridge Database. J. Med. Chem. 2004, 47, 6609-6615.
19. Cherkasov, A.; Shi, Z.; Fallahi, M.; Hammond, G. L. Successful in Silico Discovery of Novel Nonsteroidal Ligands for Human Sex Hormone Binding Globulin. J. Med. Chem. 2005, 48, 3203-3213.
20. Guner, O.; Clement, O.; Kurogi, Y. Pharmacophore Modeling and Three-Dimensional Database Searching for Drug Design Using Catalyst: Recent Advances. Curr. Med. Chem. 2004, 11, 2991-3005.
21. 2+ Signaling, Cytotoxicity and Antitumor Activity of the Herbicide Oryzalin and Its Analogues. Cancer Chemorher. Phannacol. 1997, 41, 22-28.
22. Havens, C. G.; Bryant, N.; Asher, L.; Lamoreaux, L.; Perfetto, S.; Brendle, J. J.; Werbovetz, K. A. Cellular Effects of Leishmanial Tubulin Inhibitors on L. donovani. Mol. Biochem. Parasitol. 2000, 110, 223-236.
23. Langreth, S. G.; Berman, J. D.; Riordan, G. P.; Lee, L. S. Fine-Structural Alterations in Leishmania tropica within Human Macrophages Exposed to Antileisihinanial Drugs in Vitro. J. Protozool. 1983, 30, 555-561.
24. Croft, S. L.; Brazil, R. P. Effect of Pentamidine Isethionate on the Ultrastructure and Morphology of Leishmania mexicana amazonensis in vitro. Ann. Trop. Med. Parasitol. 1982, 76, 37-43.
25. Gonçalves, A. R.; Soares, M. J.; de Souza, W.; DaMatta, R. A.; Alves, E. W. Ultrastructural Alterations and Growth Inhibition of Trypanosoma cruzi and Leishmania major Induced by Bothrops jararaca Venom. Parasitol. Res. 2002, 88, 598-602.
26. Salem, M. M. Werbovetz, K. A. Antiprotozoal Compounds from Psorothamnus polvdenius. J. Nat. Prod. 2005, 68, 108-111.
27. Bray, P. G.; Barrett, M. P.; Ward, S. A.; de Koning, H. P. Pentamidine Uptake and Resistance in Pathogenic Protozoa: Past, Present and Future. Trends Parasitol. 2003, 19, 232-239.
28. Basselin, M.; Denise, H.; Coombs, G.; Barrett, M. Resistance to Pentamidine in Leishmania mexicana involves exclusion of the drug from the mitochondrion. Antimicrob. Agents Chemother. 2002, 46, 3731-3738.
29. Mukherjee, A.; Padmanabhan, P.; Sahani, M.; Barrett, M.; Madhubala, R. Roles for Mitochondria in Pentamidine Susceptibility and Resistance in Leishmania donovani. Mol. Biochem. Parasitol. 2006, 145, 1-10.
30. Muelas-Serrano, S.; Pérez-Serrano, J.; Gómez-Barrio, A.; Arán, V. J.; Rodríguez-Caabeiro, F. Ultrastructural Alterations Induced by Nifurtimox and Another Nitro Derivative on Epimastigotes of Trypanosoma cruzi. Parasitol. Res. 2002, 88, 97-101.
31. Voigt, W.-H.; Bock, M.; Gönnert, R. Ultrastructural Observations on the Activity of Nifurtimox on the Causative Organism of Chagas' Disease 1. Trypanosoma cruzi in Tissue Cultures. Arzneim.-Forsch. 1972, 22, 1586-1589.
32. Kroemer, G.; Dallaporta, B.; Resche-Rigon, M. The Mitochondrial Death/Life Regulator in Apoptosis and Necrosis. Annu. Rev. Physiol. 1998, 60, 619-642.
33. Werbovetz, K. A.; Brendle, J. J.; Sackett, D. L. Purification, Characterization and Drug Susceptibility of Tubulin from Leishmania. Mol. Biochem. Parasitol. 1999, 98, 53-65.
34. Reynolds, E. S. The Use of Lead Citrate at High pH as an Electron-Opaque Stain in Electron Microscopy. J. Cell Biol. 1963, 17, 208-212.
35. Croft, S. L.; Neal, R. A.; Pendergast, W.; Chan, J. H. The Activity of Alkyl Phosphorylcholines and Related Derivatives against Leishmania donovani. Biochem. Pharmacol. 1987, 36, 2633-2636.