Applied Biochemistry and Biotechnology

, Volume 160, Issue 8, pp 2208–2218

Rational Approaches for Drug Designing Against Leishmaniasis

  • Anil Kumar Shukla
  • Bishal Kumar Singh
  • Sanjukta Patra
  • Vikash Kumar Dubey


Leishmaniasis has been ignored for many years mainly because it plagues remote and poor areas. However, recently, it has drawn attention of several investigators, and active research is going on for antileishmanial drug discovery. The current available drugs have high failure rates and significant side effects. Recently, liposomal preparations of amphotericin B are available and have proved to be a better drug, but they are very expensive. Miltefosine is one of the few orally administered drugs that are effective against Leishmania. However, it has exhibited teratogenicity, hence, should not be administered to pregnant women. Thus, the search for novel and improved antileishmanial drugs continue. A rational approach to design and develop new antileishmanials can be to identify several metabolic and biochemical differences between host and parasite that can be exploited as drug target. Moreover, many natural products also have significant antileishmanial activity and are yet to be exploited. In the current review, we aim to bring together various drug targets of Leishmania, recent development in the field, future prospects, and hope in the area.


Leishmaniasis Drug development Drug targets Metabolic pathways Proteins 


  1. 1.
    Myler, P. J. & Fasel, N. (2008). Leishmania: after the genome. Wymondham, UK: Caister Academic Press.Google Scholar
  2. 2.
    Alvar, J. Yactayo, S. & Bren, C. (2006). Trends in Parasitology, 2, 552–557.CrossRefGoogle Scholar
  3. 3.
    Murray, H. W. (2002). New England Journal of Medicine, 347, 1793–1794.CrossRefGoogle Scholar
  4. 4.
    Bora, D. (1999). National Medical Journal of India, 12, 62–68.Google Scholar
  5. 5.
    Dujardin, J. C. Campino, L. Canavate, C. et al. (2008). Europe. Emerging Infectious Diseases, 14, 1013–1018.CrossRefGoogle Scholar
  6. 6.
    Slappendel, R.J., & Ferrer, L. (1998). In: C. E. Greene (Ed.), Infectious diseases of the dog and cat (pp. 450–458). Philadelphia: WB Saunders Co.Google Scholar
  7. 7.
    Grosjean, N. L. Vrable, R. A. Murphy, A. J. & Mansfield, L. S. (2003). Journal of the American Veterinary Medical Association, 222, 603–606.CrossRefGoogle Scholar
  8. 8.
    Croft, S. L. & Coombs, G. H. (2003). Trends in Parasitology, 19, 502–508.CrossRefGoogle Scholar
  9. 9.
    Pearson, R. D. Jeronimo, S. M. B. & Sousa, A. (1996). Clinical Infectious Diseases, 22, 1–13.Google Scholar
  10. 10.
    Mattock, N. (1999). TDR News, 60, 1–2.Google Scholar
  11. 11.
    Sinha, P. K. Ranjan, A. Singh, V. P. Das, V. N. R. Pandey, K. Kumar, N. et al. (2006). Journal of Infection, 53, 60–64.CrossRefGoogle Scholar
  12. 12.
    Berman, J. (2003). Current Opinion in Infectious Diseases, 16, 397.CrossRefGoogle Scholar
  13. 13.
    Sundar, S. Jha, T. K. Thakur, C. P. Sinha, P. K. & Bhattacharya, S. K. (2007). New England Journal of Medicine, 356, 2571–2581.CrossRefGoogle Scholar
  14. 14.
    Dumas, C. Ouellette, M. Tovar, J. Cunningham, M. J. Fairlamb, A. H. Tamar, S. et al. (1997). EMBO Journal, 16, 2590–2598.CrossRefGoogle Scholar
  15. 15.
    Flohe, L. Hecht, H. J. & Steinert, P. (1999). Free Radical Biology & Medicine, 27, 966–984.CrossRefGoogle Scholar
  16. 16.
    Alphey, M. S. Bond, C. S. Tataud, E. Fairlamb, A. H. & Hunter, W. N. (2000). Journal of Molecular Biology, 300, 903–916.CrossRefGoogle Scholar
  17. 17.
    Bonse, S. Santelli-Rouvier, C. Barbe, J. et al. (1999). Journal of Medicinal Chemistry, 42, 5448–5454.CrossRefGoogle Scholar
  18. 18.
    Parveen, S. Khan, M. O. F. Austin, S. E. Croft, S. L. Yardley, V. Rock, P. et al. (2005). Journal of Medicinal Chemistry, 48, 8087–8097.CrossRefGoogle Scholar
  19. 19.
    Fournet, A. Barrios, A. A. Munoz, V. Hocquemiller, R. Cave, A. & Bruneton, J. (1993). Antimicrobial Agents and Chemotherapy, 37, 859–863.Google Scholar
  20. 20.
    Meiering, S. Inhoff, O. Mies, J. Vincek, A. Garcia, G. Kramer, B. et al. (2005). Journal of Medicinal Chemistry, 48, 4793–4802.CrossRefGoogle Scholar
  21. 21.
    Thronalley, P. J. Ladan, M. J. Ridgway, S. J. S. & Kang, Y. (1996). Journal of Medicinal Chemistry, 39, 3409–3411.CrossRefGoogle Scholar
  22. 22.
    Vickers, T. J. Greig, N. & Fairlamb, A. H. (2004). Proceedings of the National Academy of Sciences of the United States of America, 101, 13186–13191.CrossRefGoogle Scholar
  23. 23.
    Bringaud, F. Rivière, L. & Coustou, V. (2006). Molecular and Biochemical Parasitology, 149, 1–9.CrossRefGoogle Scholar
  24. 24.
    Haanstra, J. R. Tuil, A. V. Kesseler, P. Reijnders, W. Michels, P. A. M. Westerhoff, H. V. et al. (2008). Proceedings of the National Academy of Sciences of the United States of America, 105(46), 17718–17723.CrossRefGoogle Scholar
  25. 25.
    Michels, P. A. M. Bringaud, F. Herman, M. Hannaert, M. & Hannaert, V. (2006). Biochimica et Biophysica Acta, 1763, 1463–1477.Google Scholar
  26. 26.
    Datta, A. K. Datta, R. & Sen, B. (2008). Antiparasitic chemotherapy: tinkering with the purine salvage pathway. Advances in Experimental Medicine and Biology, 625, 116–132.CrossRefGoogle Scholar
  27. 27.
    Aronow, B. Kaur, K. McCartan, K. & Ullman, B. (1987). Molecular and Biochemical Parasitology, 22, 29–37.CrossRefGoogle Scholar
  28. 28.
    Glew, R. H. Saha, A. K. Das, S. & Remaley, A. (1988). Microbiological Reviews, 52(4), 412–432.Google Scholar
  29. 29.
    Lafon, S. W. Nelson, D. J. Berens, R. L. & Marr, J. J. (1985). Journal of Biological Chemistry, 260(17), 9660–9665.Google Scholar
  30. 30.
    Chen, M. Zhai, L. Christensen, S. B. Theander, T. G. & Kharazmi, A. (2001). Antimicrobial Agents and Chemotherapy, 45, 2023–2029.CrossRefGoogle Scholar
  31. 31.
    Torres-Santos, E. C. Sampaio-Santos, M. I. Buckner, F. S. Yokoyama, K. Gelb, M. Urbina, J. A. et al. (2009). Journal of Antimicrobial Chemotherapy, 63, 469–472.CrossRefGoogle Scholar
  32. 32.
    Salem, M. M. & Werbovetz, K. A. (2005). Antiprotozoal Compounds from Psorothamnus polydenius. Journal of Natural Products, 68, 108.CrossRefGoogle Scholar
  33. 33.
    Delorenzi, J. C. Attias, M. Gattass, C. R. Andrade, M. Rezende, C. da Cunha Pinto, A. et al. (2001). Antimicrobial Agents and Chemotherapy, 45, 1349–1354.CrossRefGoogle Scholar
  34. 34.
    Saleheen, D. Ali, S. A. & Yasinzai, M. M. (2004). Fitoterapia, 75, 9–13.CrossRefGoogle Scholar
  35. 35.
    Ngure, P. K. Tonui, W. K. Ingonga, J. Mutai, C. Kigondu, E. Nganga, Z. et al. (2009). Journal of Medicinal Plants Research, 3, 61–66.CrossRefGoogle Scholar
  36. 36.
    Singh, N. Mishra, P. K. Kapil, A. Arya, K. R. Maurya, R. & Dube, A. (2005). Journal of Ethnopharmacology, 98, 83–88.CrossRefGoogle Scholar
  37. 37.
    Misra, P. Khaliq, T. Reddy, K. P. Gupta, S. Kant, R. Maulik, P. R. et al. (2008). Journal of Antimicrobial Chemotherapy, 62, 998–1002.CrossRefGoogle Scholar
  38. 38.
    Chowdhury, A. R. Mandal, S. Mittra, B. Sharma, S. Mukhopadhyay, S. & Majumder, H. K. (2002). Medical Science Monitor, 8, BR254–BR265.Google Scholar
  39. 39.
    Chowdhury, A. R. Sharma, S. Mandal, S. Goswami, A. Mukhopadhyay, S. & Majumder, H. K. (2002). Biochemical Journal, 366(Pt 2), 653–661.CrossRefGoogle Scholar
  40. 40.
    Roy, A. Ganguly, A. BoseDasgupta, S. Das, B. B. Pal, C. Jaisankar, P. et al. (2008). Molecular Pharmacology, 74, 1292–1307.CrossRefGoogle Scholar
  41. 41.
    Singh, B. K. Sarkar, N. & Dubey, V. K. (2008). Current Trends in Biotechnology and Pharmacy, 2, 390–395.Google Scholar
  42. 42.
    Singh, B. K. Sarkar, N. Jagannadham, M. V. & Dubey, V. K. (2008). BMB Reports, 41, 444–447.Google Scholar
  43. 43.
    Akendengue, B. Roblot, F. Loiseau, P. M. Bories, C. Ngou-Milama, E. Laurens, A. et al. (2002). Phytochemistry, 59, 885.CrossRefGoogle Scholar
  44. 44.
    Fevrier, A. Ferreira, M. E. Fournet, A. Yaluff, G. Inchausti, A. Rojas de Arias, A. et al. (1999). Planta Medica, 65, 47.CrossRefGoogle Scholar
  45. 45.
    Marles, R. J. Farnsworth, N. R. & Neill, D. A. (1989). Journal of Natural Products, 52, 261.CrossRefGoogle Scholar
  46. 46.
    Hoet, S. Stevigny, C. Block, S. Opperdoes, F. Colson, P. Baldeyrou, B. et al. (2004). Planta Medica, 70, 407.CrossRefGoogle Scholar
  47. 47.
    Moretti, C. Sauvain, M. Lavaud, C. Massiot, G. Bravo, J. & Munoz, V. (1998). Journal of Natural Products, 61, 1390.CrossRefGoogle Scholar
  48. 48.
    Fournet, A. De Arias, R. A. Ferreira, M. E. et al. (2000). International Journal of Antimicrobial Agents, 13, 189–195.CrossRefGoogle Scholar
  49. 49.
    Thouvenel, C. Hocquemiller, R. & Fournet, A. (2002). Journal of Ethnopharmacology, 80, 199–202.CrossRefGoogle Scholar
  50. 50.
    Ray, S. Hazra, B. Mittra, B. Das, A. & Majumder, H. K. (1998). Molecular Pharmacology, 54, 994.Google Scholar
  51. 51.
    Camacho, M. R. Kirby, G. C. Warhurst, D. C. Croft, S. L. & Phillipson, J. D. (2002). Planta Medica, 66, 478.CrossRefGoogle Scholar
  52. 52.
    Montenegro, H. Gutierrez, M. Romero, L. I. Ortega-Barria, E. Capson, T. L. & Rios, L. C. (2003). Planta Medica, 69, 677.CrossRefGoogle Scholar
  53. 53.
    Kalla, G. Singh, M. K. & Kalla, G. (1996). Indian Journal of Dermatology Venereology and Leprology, 62, 149–151.Google Scholar
  54. 54.
    El-On, J. Jacobs, G. P. Witztum, E. & Greenblatt, C. L. (1984). Antimicrobial Agents and Chemotherapy, 26, 745. district.Google Scholar
  55. 55.
    Takahashi, M. Fuchino, H. Satake, M. Agatsuma, Y. & Sekita, S. (2004). Biological and Pharmaceutical Bulletin, 27, 921.CrossRefGoogle Scholar
  56. 56.
    Del Rayo Camacho, M. Phillipson, J. D. Croft, S. L. Yardley, V. & Solis, P. N. (2004). Planta Medica, 70, 70.CrossRefGoogle Scholar
  57. 57.
    Mbwambo, Z. H. Apers, S. Moshi, M. J. Kapingu, M. C. VanMiert, S. Claeys, M. et al. (2004). Planta Medica, 70, 706.CrossRefGoogle Scholar
  58. 58.
    Plock, A. Beyer, G. Hiller, K. Grundemann, E. Krause, E. Nimtz, M. et al. (2001). Phytochemistry, 57, 489.CrossRefGoogle Scholar
  59. 59.
    Saeidnia, S. Gohari, A. R. Uchiyama, N. Ito, M. Honda, G. & Kiuchi, F. (2004). Chemical and Pharmaceutical Bulletin, 52, 1249.CrossRefGoogle Scholar
  60. 60.
    Thiem, D. A. Sneden, A. T. Khan, S. I. & Tekwani, B. L. (2005). Journal of Natural Products, 68, 251.CrossRefGoogle Scholar
  61. 61.
    Muhammad, I. Bedir, E. Khan, S. I. Tekwani, B. L. Khan, I. A. Takamatsu, S. et al. (2004). Journal of Natural Products, 67, 772.CrossRefGoogle Scholar
  62. 62.
    Singh, N. Gupta, R. Jaiswal, A. K. Sundar, S. & Dube, A. (2009). Journal of Antimicrobial Chemotherapy, 64(2), 370–374. doi:10.1093/jac/dkp206.CrossRefGoogle Scholar
  63. 63.
    Khan, M. (2007). Drug Target Insights, 1, 129–146.Google Scholar
  64. 64.
    Benson, T. J. Mckie, J. H. Garforth, J. Borges, A. Fairlamb, A. H. & Douglas, K. T. (2008). Journal of Biochemistry, 286, 9–11.Google Scholar
  65. 65.
    Cota, B. B. Rosa, L. H. Caligiorne, R. B. Rabello, A. L. T. Almeida Alves, T. M. & Zani, C. S. (2008). FEMS Microbiology Letters, 285, 177–182.CrossRefGoogle Scholar
  66. 66.
    Heby, O. Roberts, S. C. & Ulman, B. (2005). Biochemical Society Transactions, 31, 415–419.CrossRefGoogle Scholar
  67. 67.
    Bhaumik, S. Basu, R. Sen, S. Naskar, K. & Roy, S. (2008). Vaccine, 12, 053.Google Scholar
  68. 68.
    Delfin, D. A. Morgan, E. R. Zhu, X. & Werbovetz, A. K. (2009). Bioorganic & Medicinal Chemistry, 17, 820–829.CrossRefGoogle Scholar

Copyright information

© Humana Press 2009

Authors and Affiliations

  • Anil Kumar Shukla
    • 1
  • Bishal Kumar Singh
    • 1
    • 2
  • Sanjukta Patra
    • 1
  • Vikash Kumar Dubey
    • 1
  1. 1.Department of BiotechnologyIndian Institute of Technology GuwahatiGuwahatiIndia
  2. 2.Department of BiochemistryUniversity of OuluOuluFinland

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