Host-guest chemistry for the treatment of leishmania

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Human leishmaniasis is an infectious parasitic disease endemic to about 90 countries by over 20 different Leishmaniasis species. It is spread by the bite of certain types of sandflies. The disease can present in three main ways: cutaneous (skin ulcers), mucocutaneous (ulcers in the mouth and nose), or visceral (bloodstream, liver and spleen are also affected) leishmaniasis.

Susana Santos Braga has published a mini-review on cyclodextrin-based tools against this disease.[1]

Cholesterol is needed for infection (for docking on the host cells and expressing virulence-associated proteins). Cholesterol depletion by CDs was proposed as a new therapeutic strategy for the treatment. Local treatment of cutaneous and mucocutaneous leishmaniasis with RAMEB resulted in reduced parasite load in mice inoculated with L. infantum.[2] Administration of an aqueous solution of HPBCD to mice infected with L. donovani caused inhibition of liver parasitemia when compared to the control.[3]

CDs are also used for improving the pharmaceutical properties of anti-leishmaniasis drugs. Some of them are repurposed (antifungal drugs found to be effective against leishmaniasis).  Some examples are listed in Table 1.

Table 1 CD complexation of drugs with antileshmaniasis effect (for references see the references in [1])

Drug CD Use Effect
Meglumine antimonate BCD Oral The complex is effective in oral route while the drug is poor only parenterally
Amphotericin B GCD Topical Enhanced solubility and stability
Pentamidine isethionate BCD Oral Increased pharmacological efficacy in mice (reduced parasite load)
Enrofloxacin HPBCD Enhanced solubility
2-n-Propyl-quinoline HPBCD i.v. Reduced parasitic load in mice infected by L. donovani
Posaconazole SBEBCD i.v. infusion Enhanced solubility and stability
Furazolidone BCD Enhanced solubility


  1. Santos Braga, S. (2019). Treating an old disease with new tricks: strategies based on host–guest chemistry for leishmaniasis therapy. Journal of Inclusion Phenomena and Macrocyclic Chemistry. doi:10.1007/s10847-019-00885-y
  2. Yao, C., Dixit, U.G., Barker, J.H., Teesch, L.M., Love-Homan, L., Donelson, J.E., Wilson, M.E.: Attenuation of Leishmania infantum chagasi metacyclic promastigotes by sterol depletion. Infect. Immun. 81, 2507–2517 (2013)
  3. Zhu, X., Pandharkar, T., Werbovetz, K.: Identification of new antileishmanial leads from hits obtained by high-throughput screen-ing. Antimic. Agent Chemother. 56, 1182–1189 (2012)

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