Synthetic Analogues of Irlbacholine:  A Novel Antifungal Plant Metabolite Isolated from <i>Irlbachia </i><i>Alata</i>

Lü, Qing; Ubillas, R.; Zhou, Yihong; Dubenko, L. G.; Dener, Jeffrey M.; Litvak, Joane; Phuan, Puay‐Wah; Flores, Mario; Ye, Zhijun; Gerber, R. E.; Truong, Thien; Bierer, Donald

doi:10.1021/np980425n

Cited by 27 publications

(21 citation statements)

References 12 publications

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“…Phosphocholines have structural similarities (Fig. 1) to the natural substrates of fungal PLB1 (e.g., phosphatidylcholine and lysophosphatidylcholine are the preferred substrates of this enzyme [7]), and alkyl-bis-phosphocholines are present in medicinal plants known for their antifungal properties (22). In mammalian tumor cells, miltefosine inhibits protein kinase C and the biosynthesis of phosphatidylcholine and sphingomyelin (14,15,16,32).…”

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confidence: 99%

Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis

Widmer

Wright

Obando

et al. 2006

Antimicrob Agents Chemother

140

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The alkyl phosphocholine drug miltefosine is structurally similar to natural substrates of the fungal virulence determinant phospholipase B1 (PLB1), which is a potential drug target. We determined the MICs of miltefosine against key fungal pathogens, correlated antifungal activity with inhibition of the PLB1 activities (PLB, lysophospholipase [LPL], and lysophospholipase-transacylase [LPTA]), and investigated its efficacy in a mouse model of disseminated cryptococcosis. Miltefosine inhibited secreted cryptococcal LPTA activity by 35% at the subhemolytic concentration of 25 M (10.2 g/ml) and was inactive against mammalian pancreatic phospholipase A2 (PLA 2 ). At 250 M, cytosolic PLB, LPL, and LPTA activities were inhibited by 25%, 51%, and 77%, respectively. The MICs at which 90% of isolates were inhibited (MIC 90 s) against Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, Cryptococcus gattii, Aspergillus fumigatus, Fusarium solani, Scedosporium prolificans, and Scedosporium apiospermum were 2 to 4 g/ml. The MICs of miltefosine against Candida tropicalis (n ‫؍‬ 8) were 2 to 4 g/ml, those against Aspergillus terreus and Candida parapsilosis were 8 g/ml (MIC 90 ), and those against Aspergillus flavus (n ‫؍‬ 8) were 2 to 16 g/ml. Miltefosine was fungicidal for C. neoformans, with rates of killing of 2 log units within 4 h at 7.0 M (2.8 g/ml). Miltefosine given orally to mice on days 1 to 5 after intravenous infection with C. neoformans delayed the development of illness and mortality and significantly reduced the brain cryptococcal burden. We conclude that miltefosine has broad-spectrum antifungal activity and is active in vivo in a mouse model of disseminated cryptococcosis. The relatively small inhibitory effect on PLB1 enzyme activities at concentrations exceeding the MIC by 2 to 20 times suggests that PLB1 inhibition is not the only mechanism of the antifungal effect.

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confidence: 99%

Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis

Widmer

Wright

Obando

et al. 2006

Antimicrob Agents Chemother

140

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“…Irlbachia alata, has been traditionally used as antimalarial in the French Guiana (Bertani et al, 2005) and one novel phosphatidylcholine, irlbacholine isolated from this specie, has been used as precursor for synthetic analogs with antifungal activity (Lu et al, 1999). Calathea warscewiczii is used by the Panama traditional medicine for several diseases (Gupta et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic and antiradical activities of plants from Venezuelan Amazon

Rodrı́guez

Hasegawa

González-Mujica

et al. 2008

Rev. bras. farmacogn.

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RESUMO: "Atividades antidiabética e anti-radicalar de plantas da Amazônia venezuelana".Os extratos aquoso e etanólico derivados de doze espécies coletadas na Amazônia venezuelana foram testados quanto à atividade antioxidante utilizando um radical DPPH e o efeito inibitório sobre a hidrólise de glicose-6-fosfato nos microssomas intactos e perturbados. Sem exceção, todos os extratos inibiram, em maior ou menor grau, a atividade enzimática microssomal de G-6-Pase, resultando em maior inibição nos microssomas intactos do que nos perturbados. Unitermos: Plantas amazônicas, atividade antidiabética, atividade anti-radicalar, glicose-6-fosfatase. ABSTRACT:The aqueous and ethanol extracts derived from twelve plant species collected in the Venezuelan Amazon have been tested for antioxidant activity using a DPPH radical and inhibitory effect on the hydrolysis of glucose-6-phosphate in intact and disrupted microsomes. Without exception, all the extracts inhibited, to a greater or lesser degree, microsomal G-6-Pase enzymatic activity, resulting in greater inhibition on intact microsomes than on disrupted ones. Marked effects were observed for aqueous and ethanol extracts of: Tontelea ovalifolia, Gustavia pulchra, Phthirusa verruculosa, Phthirusa castillana, Psittacanthus acimarius, Tetrapterys styloptyera and Vismia japurensis. Ethanol extracts were more effective DPPH radical scavengers than the corresponding aqueous extracts in all the cases. The ethanol extract of Endlicheria anomala and the aqueous extract of Phthirusa verruculosa, showed the best IC 50 with 100 and 250.0 ppm, respectively. The Kobs calculated for the alcoholic extracts were lower than those of the aqueous extracts for the same species, except Psittacanthus acimarius. These results could be related to different concentrations, or more likely different compositions of active principles in both extracts.

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“…azadirachtin from Azadirachta indica, pyrethrum from Chrysanthemum cinerariaefolium and carvone from Carum carvi have been formulated and are in regular use in the management of different agricultural pests (Varma & Dubey 1999;Varma et al 2002). Much work has been carried out on the effects of medicinal and aromatic plant extracts against various fungi (Lu et al 1999), but their effect upon dermatophytes and related fungi is unexplored. Dermatophytes are known to cause superficial skin infections like scabies (Ganapathiraman et al 1979).…”

Section: Introductionmentioning

confidence: 99%

Isolation, Identification and Study of Antimicrobial Property of a Bioactive Compound in an Indian Medicinal Plant Acalypha indica (Indian-Nettle)

Solomon

Subramaniam

Jayaraj

2005

World J Microbiol Biotechnol

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Fresh, dried and powdered samples of leaf, stem and root of Acalypha indica were subjected to fractional distillation in a soxhlet apparatus using solvents such as hexane, chloroform, acetone and methanol. The plant extracts and a synthetic antifungal compound, Clotrimazole (authentic standard) were subjected to TLC and HPLC analyses. The R f (relative front) value of Clotrimazole was 0.371. The plant's leaf, root and stem extracts also gave distinct spots respectively at R f value of 0.371 ± 0.0009. In HPLC, the TLC-separated active compound and Clotrimazole resolved at 1.90 ± 0.2 min (retention time). The amounts of active compound present in root, leaf and stem extracts were 538, 415 and 171 lg/g respectively. From the results of our study, we infer that the active compound isolated from Acalypha indica is more potent in controlling Candida albicans, Aspergillus niger and Escherichia coli. The Active compound present in the plant had more than 100% activity when compared to standard Clotrimazole.

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Synthetic Analogues of Irlbacholine: A Novel Antifungal Plant Metabolite Isolated from Irlbachia Alata

Cited by 27 publications

References 12 publications

Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis

Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis

Antidiabetic and antiradical activities of plants from Venezuelan Amazon

Isolation, Identification and Study of Antimicrobial Property of a Bioactive Compound in an Indian Medicinal Plant Acalypha indica (Indian-Nettle)

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