Activity of compound G2 isolated from alfalfa roots against medically important yeasts

Polacheck, Itzhack; Zehavi, Uri; Naim, Michael; Levy, M.; Evron, Ruth

doi:10.1128/aac.30.2.290

Cited by 29 publications

(11 citation statements)

References 17 publications

(12 reference statements)

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“…Compound 6 has been reported to have antifungal effects against Trichoderma viride, Aspergillus niger and against several medically important yeasts such as C. albicans. [39][40][41][42] Its mode of action against Saccharomyces cerevisiae seems to be different from that described for polyene antibiotics. 44 As compared to other saponins aglycones that are inactive, the low MIC value of 7 might be rationalised by the presence of the carboxylic acid function in position 4 that gives polar properties to the molecules.…”

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confidence: 83%

Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa and In Depth Investigation of Their in vitro and in vivo Antifungal Activities

Favre-Godal¹,

Dorsaz²,

Marcourt³

et al. 2016

J. Braz. Chem. Soc.

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As a part of a broad screening of antifungal agents from plant origin, crude extracts from Panamanian plants having related types of constituents displayed significant activities in an agar overlay thin layer chromatography assay against a susceptible strain of Candida albicans. These were the methanolic extract of the leaves of Schefflera systyla and Odontadenia puncticulosa and of the stems of Conostegia speciosa, that are species not previously investigated from a phytochemical viewpoint. For all plants, high-performance liquid chromatography (HPLC) antifungal activity based profiling allowed the rapid localization of antifungal agents that were further obtained by targeted isolation procedure by semi-preparative HPLC or medium pressure liquid chromatography (MPLC) after LC gradient transfer. Different hederagenin saponins and one aglycone were found to be responsible for the antifungal activities of the extracts. Alpha-hederin was the antifungal of S. systyla, pulsatilla saponin D and 3β-O-[β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranosylhederagenin of O. puncticulosa and arjunolic acid of C. speciosa. Their minimal inhibitory concentration (MIC) against planktonic and biofilm cells of C. albicans were determined. Alpha-hederin was the most potent compound with a MIC of 4 µg mL -1 . Structurally related compounds (hederagenin, medicagenic acid 3-O-β-D-glucopyranoside and medicagenic acid) were used as standards and tested for comparison purposes. In order to better estimate the potential of these triterpenoids as antifungal agents, their cytological effects on C. albicans were determined by transmission electron microscopy (TEM) and the in vivo activity of alpha-hederin, medicagenic acid 3-O-β-D-glucopyranoside and medicagenic acid was evaluated for the first time in the Galleria mellonella larvae model. Keywords: triterpenoids, microfractionation, antifungal, Candida species, Galleria mellonella IntroductionFungal infections have recently increased worldwide and cause high morbidity and mortality rates among different groups of human patients. 1 The development of drug resistance in fungal pathogens compromises the efficacy of the limited number of therapeutic agents. 2The main fungal opportunistic human pathogens are Candida spp., and among them, the most common species is Candida albicans. 3 In the USA, Candida species are the fourth cause of nosocomial bloodstream infections. 4,5 Over 400,000 candidiasis infections are declared per year worldwide. 6 Moreover, Candida species display a tendency Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa J. Braz. Chem. Soc. 444 to grow as biofilms on implanted medical devices such as a central venous catheter. 7 Biofilm cells exhibit up to a 1,000-fold increase in resistance as compared to their planktonic counterparts 8 which may contribute to therapeutic failures. 9 These facts make urgent the need to identify new chemical entities that may lead to the disc...

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confidence: 83%

Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa and In Depth Investigation of Their in vitro and in vivo Antifungal Activities

Favre-Godal¹,

Dorsaz²,

Marcourt³

et al. 2016

J. Braz. Chem. Soc.

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“…Compound G2 isolated from alfalfa roots is active in vitro against plant pathogenic fungi (4), medically important yeasts (8,9), and dermatophytes (2). This compound is the glucp derivative of medicagenic acid, the major saponin aglycon occurrng in alfalfa roots (1).…”

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Activity of compound G2 isolated from alfalfa roots in experimental dermatophyte infection

Evron

Guizie

Zehavi

et al. 1990

Antimicrob Agents Chemother

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Compound GZ isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applictions, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of the untreated lesions which healed spontaneously (P < 0.01).Dermatophytes, a closely related group of keratinophilic fungi, cause a wide variety of skin, hair, and nail infections. These fungi have a worldwide distribution and are among the most common infectious agents of humans and animals. They cause both acute inflammatory and chronic noninflammatory types of infection (11). The limited number of available effective antimycotic drugs has stimulated a search for new agents.Compound G2 isolated from alfalfa roots is active in vitro against plant pathogenic fungi (4), medically important yeasts (8, 9), and dermatophytes (2). This compound is the glucp derivative of medicagenic acid, the major saponin aglycon occurrng in alfalfa roots (1). Medicagenic acid, its dimethyl esters, and the malto derivative thereof were also effective against plant pathogenic fungi (46).Compound G2 has a strong affinity for ergosterol, and its fungicidal effect was probably due to increased membrane permeability which caused leakage of ions and small molecules. When sterols were added to the medium, reduced susceptibility of fungi to the drug was observed (M. Levi, I. Polacheck, M. Guizie, U. Zehavi, M. Naim, and R. Evron, submitted for publication).This study describes the topical use of compound G2 for experimental dermatophytosis in the guinea pig, using a model previously shown to simulate human inflammatory fungal infections caused by zoophilic dermatophytes such as Trichophyton mentagrophytes var. granulare and Microsporum canis (11,12, 14). A clinical isolate of T. mentagrophytes var. granulare was used. It was identified by conventional methods (10) and maintained on slants of potato dextrose agar prepared from 20 g of potato infusion (Difco Laboratories), 20 g of dextrose (Difco), and 2.5 g of yeast extract (Difco) containing 50 ,ig of chloramphenicol and 0.5 g of cycloheximide per liter, at pH 5.6. A suspension containing 5 x 107 particles (spores and hyphae) was prepared as previously described (2). Compound G2 was prepared at a concentration of 2.5 mg/ml in a vehicle solution of 0.1% (wt/vol) polyethylene glycol in 2 mM sodium hydroxide, as previously described (9).The backs and flanks of Duncan Hartley female guinea pigs weighing 200 to 300 g were shaven. The exposed skin was lightly abraded with sandpaper to facilitate the adhesion of fungal elements, cleansed with 70%o ethanol, covered with fungal suspension, and occluded. After 3 days, scrapings of * Corresponding author.scales from the infected areas were examined microscopically in 30% KOH and cultured on potato dextrose agar slants. When infection was verified, treatment with compound G2 was started. Compound G2 was applied once daily to the infected le...

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“…G2 was fungicidal at 5 to 22 ,ug/ml. Structure and toxicity relations are discussed.The widespread occurrence of skin, nail, and hair infections caused by dermatophytes, coupled with the limited number of available drugs effective against them, has led to a search for new antimycotic agents.A recently isolated compound, 02, which was extracted from the roots of alfalfa plants, showed considerable activity against plant pathogenic fungi (6) and medically important yeasts (8,9). Compound G2 was identified as the gluco derivative of medicagenic acid (MA), the major occurring saponin aglycon of alfalfa roots (1).…”

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confidence: 99%

“…A recently isolated compound, 02, which was extracted from the roots of alfalfa plants, showed considerable activity against plant pathogenic fungi (6) and medically important yeasts (8,9). Compound G2 was identified as the gluco derivative of medicagenic acid (MA), the major occurring saponin aglycon of alfalfa roots (1).…”

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confidence: 99%

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Activities of compound G2 isolated from alfalfa roots against dermatophytes

Evron

Polacheck

Guizie

et al. 1988

Antimicrob Agents Chemother

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An antimycotic agent, compound G2, isolated from alfalfa roots exhibited considerable activity against the six most common dermatophytes. MICs in agar and broth dilutions ranged from 10 to 30 ,ug/ml and from 2 to 10 ,ug/mIl, respectively. G2 was fungicidal at 5 to 22 ,ug/ml. Structure and toxicity relations are discussed.The widespread occurrence of skin, nail, and hair infections caused by dermatophytes, coupled with the limited number of available drugs effective against them, has led to a search for new antimycotic agents.A recently isolated compound, 02, which was extracted from the roots of alfalfa plants, showed considerable activity against plant pathogenic fungi (6) and medically important yeasts (8,9). Compound G2 was identified as the gluco derivative of medicagenic acid (MA), the major occurring saponin aglycon of alfalfa roots (1). It has been suggested that the antimycotic activity of compound G2 is related to the ability of alfalfa saponins to complex with sterols and that fungi susceptible to these compounds contain relatively higher proportions of sterols in their membranes (1). Numerous crude saponin extracts from other plants have also been shown to possess ant'imycotic activity (3, 4).The present study describes the fungicidal effect of compound 'G2, which was found to' be superior to all other chemically related compounds (listed below) against the six most common dermatophytes.Dermatophytes 'were isolated from clinical specimens taken from various body sites of patients. Dermatophyte isolates were identified by conventional methods (11) We also modified the method of susceptibility testing by broth dilution (12). Dermatophyte suspensions were prepared as described above. A 10-,il bacteriological loop of suspension was transferred to potato dextrose broth and incubated at 26°C. After 5 to 7 days, the mycelium was homogenized and filtered, and counting was done as described above. The tests were performed in test tubes containing different concentrations of G2 (between 5 and 30 ,ug/ml) and inocula of 105 particles in 4 ml of potato dextrose broth.Two inoculated tubes containing drug-free medium were included in each experiment. Three glass beads were added to each tube to enhance mixing. All tubes were incubated loosely capped at 30°C in a shaker.Susceptibility was esti'mated after 5 to 7 days of growth by determining the MIC as the lowest drug concentration at which the broth remained clear.The minimum fungicidal concentration was determined by assaying the CFU on PDA plates. Three 50-,u samples obtained immediately after vortex mixing from the tubes showing no growth were subcultured on PDA. The minimum fungicidal concentration was established as the lowest concentration of drug with which all subcultures were absolutely negative (exceeding the 99.9% killing endpoint).The antifungal effect of compound G2 was tested on numerous isolates of six species of dermatophytes by the agar and broth dilution method's. This provided in vitro assessment of both the MICs and minimum fungicidal concentrat...

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Activity of compound G2 isolated from alfalfa roots against medically important yeasts

Cited by 29 publications

References 17 publications

Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa and In Depth Investigation of Their in vitro and in vivo Antifungal Activities

Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa and In Depth Investigation of Their in vitro and in vivo Antifungal Activities

Activity of compound G2 isolated from alfalfa roots in experimental dermatophyte infection

Activities of compound G2 isolated from alfalfa roots against dermatophytes

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