Antileishmanial

Antiknock agent Antiknock index Antileishmanial agent Antileukemic activity Antdon... 

Miltefosine, an alkylphosphocholine derivative, is a new antileishmanial drug and the first effective oral treatment of visceral leishmaniasis. However, there are concerns regarding teratogenicity, rapid emergence of resistance, and variable cure rates, possibly due to species differences in drug sensitivity. The mechanism of action of miltefosine is not known. 

Pentavalent antimonial drugs have been the cornerstone of antileishmanial therapy for more than 70 years, in spite of their general toxicity causing a wide range of side effects [2]. Pentavalent antimonial drugs have to be administered parenterally, which is a painful procedure. Meanwhile, resistance is widespread. In India,... 

Miltefosin The antileishmanial activity of this anticancer drug was discovered in the mid-1980s. It is the first oral drug available to treat visceral and cutaneous/mucocutaeous leishmaniasis. However, the registration process is slow. 

Di GC, De MM, Chiron J, Delmas F (2005) Synthesis and antileishmanial activities of 4, 5-di-substituted acridines as compared to their 4-mono-substituted homologues. Bioorg Med Chem 13 5560-5568... 

A series of aryltriazolylhydroxamates were reported as histone deacetylase (HDAC) inhibitors, exemplified by 49 (HDAC IC50 = 9.6 nM) which exhibited activity (L.d. IC50 = 4.5 pg/ mL) in an in vitro antileishmanial assay [48]. 

Licochalcone (50) is a natural product that is isolated from the roots of Chinese liquorice and is reported to have antileishmanial activity [49]. A series of chromene-substituted chalcones related to licochalcone have been reported to have antileishmanial activity [50]. Compound 51 was reported to have an IC50 of 1.2 pM against Leishmania major promastigotes versus meglumine antimoniate (IC50 =30 pM). Various compounds related to 51 have potent antileishmanial activity (IC50 < 3 pM) with potency similar to 51, but they did not show cytotoxicity. 

N- and O-Substituted terpenyl pyrimidines <05EJM552> as well as dihydropyrido[2,3-rf]-pyrimidines <05BMC6678> were prepared as antileishmanial agents. 5-Alkynyl- and 6-alkyl-furo[2,3-rf]pyrimidine acyclic nucleosides <05BMC1239>, acyclic furo- and... 

Delorenzi JC, Attias M, Gattass CR, Andrade M, Rezende C, Pinto AC, Henriques AT, Bou-Habib DC and Saraiva EM. 2001. Antileishmanial activity of indole alkaloid from Peschiera australis. Antimicrob Agents Chemother 45(5) 1349-1354. 

Stager, S., et al., Both intcrlcukin-4 (IL-4) and IL-4 receptor alpha signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity, Infect. Immun. 71, 8, 4804, 2003. 

Kuryshev, Y.A., Wang, L., Wible, B.A., Wan, X. and Ficker, E. (2006) Antimony-based antileishmanial compounds prolong the cardiac action potential by an increase in cardiac calcium currents. Molecular Pharmacology, 69, 1216-1225. 

In one experiment, LC-AmB was compared with AmBisome (small unilamellar liposomes). LC-AmB was found to have an ED50 of 0.19 mg/kg and an ED90 of 0.51 mg/kg, whereas for AmBisome both these parameters were below 0.20 mg/kg, the lowest dose tested. In another experiment, LC-AmB was compared with Abelcet and showed a better reduction of parasite burden after three injections of 1 mg/kg, but there were not sufficient data to allow ED50 values to be calculated (22). Therefore, we can conclude that this new AmB formulation retains antileishmanial activity in vivo, but it is difficult to position it with respect to other formulations. 

Loiseau PM, et al. Design and antileishmanial activity of amphotericin B-loaded stable ionic amphiphile biovector formulations. Antimicrob Agents Chemother... 

Larabi M, et al. Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B. Antimicrob Agents Chemother 2003 47 3774. 

Habtemariam S. (2003) In vitro antileishmanial effects of antibacterial diterpenes from two Ethiopian Premna species P schimperi and P. olig-otricha. BMC Pharmacology 3 6, doi 10.1186/1471-2210-3-6. 

Christensen, S.B. et ah. An antileishmanial chalcone from Chinese licorice roots, Planta Med., 60, 121, 1994. 

Castillo D, Arevalo J, Herrera F, Ruiz C, Rojas R, Rengifo E, Vaisberg A, Lock D, Le-mesre JL, Gomitzka H, Sauvain M. Spirolactone Iridoids might be responsible for the Antileishmanial Activity of a Peruvian Traditional Remedy Made with Himatanthus sucuuba (Apocynaceae). Journal of Ethnopharmacology 2007 112(2) 410-414. 

Antibacterial activity in serum of the 3,5-diamino translation inhibitor, compound 511 was determined against Escherichia coli and Pseudomonas aeruginosa (08BML3369). Antileishmanial and cytotoxicity toward macrophages of 2,3-dihydro-5H-pyrido[l,2,3-de][l,4]benzoxazin-5-one was measured (09EJM845). 

Foumet and Munoz published a review on natural products as trypanocidal, antileishmanial and antimalarial drugs. Among the active natural products, they include some naphthoquinones related to lapachol [194]. 

Iwli et al [97] have reports based on the evaluation of plant-extract of D. multiradiata for antileishmanial activity using a mechanism-based radiorespirometric micro-technique. Extracts were found to be active at concentrations of 50 pg/ml or less against a visceral leishmania isolate. A number of Dorstenia species used traditionally as anti-snake venom were subjected to a pharmacological screening process and were found to possess analgesic and anti-inflammatory activities [98]. Many of the flavonoids isolated from African Dorstenia show moderate to good antioxidant activities [Croft, unpublished results]. The cytotoxic properties of... 

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