Synthesis, antifungal and antimicrobial activity of alkylphospholipids

Obando, Daniel; Widmer, Fred; Wright, Lesley C.; Sorrell, Tania C.; Jolliffe, Katrina A.

doi:10.1016/j.bmc.2007.05.028

Cited by 35 publications

(39 citation statements)

References 30 publications

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“…All fi rst and second drug choices, including miltefosine, have high toxicity, require parenteral use, have high rates of relapse and drug resistance, and ultimately lead to treatment failure, especially in immunocompromised patients who desperately require new therapies 3 . Miltefosine (hexadecylphosphocholine) is an alkylphosphocholine, originally developed for the treatment of cancer, which was discovered to possess antifungal, antiamoebic, and leishmanicidal activity 4,5 . The drug exerts its cytotoxic effect by interfering with the metabolism of membrane phospholipids, altering the composition, permeability, stability, and fluidity of the cell membrane, subsequently inducing apoptos is 3,6 .…”

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confidence: 99%

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

Santarem

Greggianin

Debastiani

et al. 2014

Rev. Soc. Bras. Med. Trop.

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Introduction:The treatment of leishmaniasis ischallenging, given the diffi culties in drug administration and resistance. Therefore, we chose to test the effi cacy of miltefosine combined with pentoxifylline. Methods: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/ kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. Results: The number of viable Leishmania reduced signifi cantly within the miltefosine-pentoxifylline group (p < 0.05). Conclusions: There is hope that a viable treatment exists for Leishmania infection.

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confidence: 99%

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

Santarem

Greggianin

Debastiani

et al. 2014

Rev. Soc. Bras. Med. Trop.

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“…A hydrophobic chain in the miltefosine analogs with 16 to 18 carbon atoms is necessary for antifungal activity. 16 Reduction of the alkyl chain length to 12 carbon atoms, 16,17 increasing the chain length to 22 carbon atoms, 8 or insertion of ester/amide functionalities in the middle of this chain 16 significantly reduces the antifungal activity. Structurally more complex alkylglycerophosphocholines exhibit moderate activities against C. albicans and C. neoformans, when compared with alkylphosphocholine derivatives.…”

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confidence: 99%

“…Structurally more complex alkylglycerophosphocholines exhibit moderate activities against C. albicans and C. neoformans, when compared with alkylphosphocholine derivatives. 16 Extensive modification of the N-substitution and the C2 unit of the choline moiety (head group) resulted in a large number of compounds, [17][18][19] some of which showed activities more potent than erucylphosphocholine 19 that is 8-fold less potent than miltefosine. 16 Within this class, octadecylphosphocholine demonstrates as much as a 4-fold increase in in vitro potency against C. albicans when compared to miltefosine.…”

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confidence: 99%

“…16 Extensive modification of the N-substitution and the C2 unit of the choline moiety (head group) resulted in a large number of compounds, [17][18][19] some of which showed activities more potent than erucylphosphocholine 19 that is 8-fold less potent than miltefosine. 16 Within this class, octadecylphosphocholine demonstrates as much as a 4-fold increase in in vitro potency against C. albicans when compared to miltefosine. 16 It appears that the intact head group or the presence of at least two small N-methyl groups plays a key role for antifungal activity.…”

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confidence: 99%

“…16 Within this class, octadecylphosphocholine demonstrates as much as a 4-fold increase in in vitro potency against C. albicans when compared to miltefosine. 16 It appears that the intact head group or the presence of at least two small N-methyl groups plays a key role for antifungal activity.…”

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confidence: 99%

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Synthesis and Antifungal Activities of Miltefosine Analogs

Ravu¹,

Yl²,

Jacob³

et al. 2013

Planta Med

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Miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. To further explore the potential of this class of compounds for the treatment of systemic mycoses, nine analogs (3a-3i) were synthesized by modifying the choline structural moiety and the alkyl chain length of miltefosine. In vitro testing of these compounds against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Aspergillus fumigatus, and Cryptococcus neoformans revealed that Nbenzyl-N,N-dimethyl-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3a), N,N-dimethyl-N-(4-nitrobenzyl)-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3d), and N-(4-methoxybenzyl)-N,N-dimethyl-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3e) exhibited minimum inhibitory concentrations (MIC) of 2.5-5.0 μg/mL against all tested pathogens, when compared to miltefosine with MICs of 2.5-3.3 μg/mL. Compound 3a showed low in vitro cytotoxicity against three mammalian cell lines similar to miltefosine. In vivo testing of 3a and miltefosine against C. albicans in a mouse model of systemic infection did not demonstrate efficacy. The results of this study indicate that further investigation will be required to determine the potential usefulness of the alkylphosphocholines in the treatment of invasive fungal infections.

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Synthesis, aggregation properties, and antiprotozoal activity of heterocyclic heterogemini surfactants

Lukáč

Timko

Mrva

et al. 2010

Heteroatom Chemistry

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A series of four heterogemini surfactants have been synthesized: 2-decyl [dodecyl(dimethyl)ammonio]ethyl phosphate, decyl 2-(1-dodecylpyrrolidinio-1-yl)ethyl phosphate, decyl 2-(1-dodecylpiperidinio-1-yl)ethyl phosphate, and decyl 2-(1-dodecylmorpholinio-1-yl)ethyl phosphate. Antiprotozoal activity of prepared compounds against Acanthamoeba lugdunensis was investigated. Decyl 2-(1-dodecylpyrrolidinio-1-yl)ethyl phosphate exhibited the best trophocidal activity. The activities of heterogemini surfactants were compared with their aggregation properties. C

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Synthesis, antifungal and antimicrobial activity of alkylphospholipids

Cited by 35 publications

References 30 publications

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

Synthesis and Antifungal Activities of Miltefosine Analogs

Synthesis, aggregation properties, and antiprotozoal activity of heterocyclic heterogemini surfactants

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