Antiprotozoal Drugs

Black, Adrienne T.; McManus, Dayna; Afolabi, Olawale D.; Ray, Sidhartha D.

doi:10.1016/bs.seda.2018.08.004

Cited by 4 publications

(1 citation statement)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, prolonged treatment schemes, parenteral administration, noncompliance and abandonment of prescribed treatment lead to the emergence of drug-resistant parasites [6,7,9]. Therefore, there is a need for new therapeutic alternatives that are more effective and efficient in terms of parasite elimination and disease resolution and that are safer for patients in terms of better adherence and fewer toxic effects [10,11].…”

Section: Introductionmentioning

confidence: 99%

Antileishmanial activity of synthetic analogs of the naturally occurring quinolone alkaloid N-methyl-8-methoxyflindersin

et al. 2020

View full text Add to dashboard Cite

Leishmaniasis is a neglected, parasitic tropical disease caused by an intracellular protozoan from the genus Leishmania. Quinoline alkaloids, secondary metabolites found in plants from the Rutaceae family, have antiparasitic activity against Leishmania sp. N-methyl-8-methoxyflindersin (1), isolated from the leaves of Raputia heptaphylla and also known as 7-methoxy-2,2-dimethyl-2H,5H,6H-pyran[3,2-c]quinolin-5-one, shows antiparasitic activity against Leishmania promastigotes and amastigotes. This study used in silico tools to identify synthetic quinoline alkaloids having structure similar to that of compound 1 and then tested these quinoline alkaloids for their in vitro antiparasitic activity against Leishmania (Viannia) panamensis, in vivo therapeutic response in hamsters suffering from experimental cutaneous leishmaniasis (CL), and ex vivo immunomodulatory potential in healthy donors’ human peripheral blood (monocyte)-derived macrophages (hMDMs). Compounds 1 (natural), 2 (synthetic), and 8 (synthetic) were effective against intracellular promastigotes (9.9, 3.4, and 1.6 μg/mL medial effective concentration [EC50], respectively) and amastigotes (5.07, 7.94, and 1.91 μg/mL EC50, respectively). Compound 1 increased nitric oxide production in infected hMDMs and triggered necrosis-related ultrastructural alterations in intracellular amastigotes, while compound 2 stimulated oxidative breakdown in hMDMs and caused ultrastructural alterations in the parasite 4 h posttreatment, and compound 8 failed to induce macrophage modulation but selectively induced apoptosis of infected hMDMs and alterations in the intracellular parasite ultrastructure. In addition, synthetic compounds 2 and 8 improved the health of hamsters suffering from experimental CL, without evidence of treatment-associated adverse toxic effects. Therefore, synthetic compounds 2 and 8 are potential therapeutic candidates for topical treatment of CL.

show abstract