Drug combinations as effective anti-leishmanials against drug resistant Leishmania mexicana

Humera Ahmed, Charlotte R. Curtis, Sara Tur-Gracia, Toluwanimi O. Olatunji, Katharine C. Carter, Roderick A. M. Williams*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
2 Downloads (Pure)

Abstract

Leishmania is a parasite that causes the disease leishmaniasis, and 700,000 to 1 million new cases occur each year. There are few drugs to treat the disease and drug resistance in the parasite is limiting the clinical utility of existing drugs. One way to combat drug resistance is to use combination rather than monotherapy. In this study we have compared the effect of single and combination treatment with four different compounds i.e. alkylphosphocholine analogues APC12 and APC14, miltefosine (MIL), ketoconazole (KTZ), and amphotericin B (AmpB), on the survival of Leishmania mexicana wild-type promastigotes and a cell line derived from the WT with induced resistance to APC12 (C12Rx). Combination treatment with APC14 and APC16 had a synergistic effect in killing WT while KTZ and APC12 or APC14 or APC12 and APC14 had synergistic effect against C12Rx. More than >90% killing occurred using APC12 alone at >1mg/ml against C12Rx strain, however combinations with APC14 produced similar killing using APC12 at 0.063mg/ml-0.25mg/ml and APC14 at 0.003mg/ml0.5mg/ml. These results show that combination therapy can negate induced drug resistance in L. mexicana and that using this type of screening system could accelerate the development of drug combinations for clinical use.
Original languageEnglish
Pages (from-to)905-912
Number of pages8
JournalRSC Medicinal Chemistry
Volume11
Issue number8
DOIs
Publication statusPublished - 2 Jul 2020

Keywords

  • parasites
  • Leishmania
  • drug resistance
  • drug combinations

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