Antifungal amides from Piper arboreum and Piper tuberculatum

In continuation of our study of the Piperaceae we have isolated several amides, mainly those bearing isobutyl, pyrrolidine, dihydropyridone and piperidine moieties. Bioactivity-guided fractionation of extracts from leaves of Piper arboreum yielded two new amides, N-[10-(13,14-methylenedioxyphenyl)-7(E),9(Z)-pentadienoyl]-pyrrolidine (1), arboreumine (2) together with the known compounds N-[10-(13,14-methylenedioxyphenyl)-7(E)-pentaenoyl]-pyrrolidine (3) and N-[10-(13,14-methylenedioxyphenyl)-7(L, 9(E)-pentadienoyl]-pyrrolidine (4). Catalytic hydrogenation of 3 yielded the amide iV-[10-(13,14-methylenedioxyphenyl)-pentanoyl]-pyrrolidine (5). We also have isolated six amides (6-11) and two antifungal cinnamoyl derivatives (12, 13) from seeds and leaves of Piper tuberculatum. Compounds 1-11 showed antifungal activity as determined by direct bioautography against Cladosporium sphaerospermum while compounds 3-4 and 6-13 also showed antifungal activity against C. cladosporioides. (C) 2002 Published by Elsevier B.V. Ltd.

Prevalence and in vitro antifungal susceptibility of Candida spp isolated from clinical specimens in São Paulo, Brazil

We examined the prevalence and the in vitro susceptibility to antifungal drugs of Candida spp isolated from clinical specimens at our university hospital in São Paulo, Brazil. Among 6,417 samples studied, positive cultures, were obtained from 222 (3.5%) most of them (68%) from the pediatric unit and nursery. Candida albicans and Candida parapsilosis were the most frequent species and the susceptibility patterns of a panel of 130 isolates to amphotericin B, ketoconazole and fluconazole. showed that the order of antifungal efficacy was amphotericin B > ketoconazole > fluconazole.

nor-Lignans from the leaves of Styrax ferrugineus (Styracaceae) with antibacterial and antifungal activity

Chemical examination of the leaves of Styrax ferrugineus yielded 5-[3'-(β-D-glucopyranosyloxy)propyl]-7-methoxy-2-(3',4'-dime-thoxyphenyl) benzofuran, along with the known nor-lignans 5-(3'-hydroxypropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl) benzofuran, 5-(3'-hydroxypropyl)-7-methoxy-2-(3',4'-dimethoxyphenyl)benzofuran, 5-[3'-(β-D-glucopyranosyloxy)propyl]-7-methoxy-2-(3', 4'-methylenedioxyphenyl)benzofuran and the lignan, dihydrodehydrodiconiferyl alcohol. All arylpropanoids isolated showed antibacterial and antifungal activities. The structures of the isolates were established by spectroscopic analysis. (C) 2000 Elsevier Science Ltd.

Antifungal activity of propolis on different species of Candida

Propolis is a resinous material collected by bees from the buds or other parts of plants. It is known for its biological properties, having antibacterial, antifungal and healing properties. The antifungal activity of propolis was studied in sensitivity tests on 80 strains of Candida yeasts: 20 strains of Candida albicans, 20 strains of Candida tropicalis, 20 strains of Candida krusei and 15 strains of Candida guilliermondii. The yeasts showed a clear antifungal activity with the following order of sensitivity: C. albicans > C. tropicalis > C. krusei > C. guilliermondii. Patients with full dentures who used a hydroalcoholic propolis extract showed a decrease in the number of Candida.

In vitro antifungal susceptibility of Candida spp. isolates from patients with chronic periodontitis and from control patients

Superinfection by Candida can be refractory to conventional periodontal treatments in specific situations, such as in immunocompromised patients. In these cases, the systemic therapy with antifungal drugs could be indicated. The aim of this study was to analyse antifungal susceptibility of Candida spp. strains isolated from chronic periodontitis patients and from control individuals. A total of 39 C. albicans isolates, 9 C. tropicalis, 2 C. glabrata and 5 Candida spp. from control individuals and 30 C. albicans, 3 C. tropicalis and 2 C. glabrata from periodontitis patients were tested. In the control group, 1 isolate of C. glabrata was resistant to ketoconazole and 1 Candida spp. was resistant to amphotericin B, ketoconazole and miconazole. Among the isolates of periodontitis group, 1 (3.33%) C. albicans isolate was resistant to flucytosine and ketoconazole. According to the obtained results, it could be concluded that fluconazole was the most effective drug against the several Candida species studied. There were not expressive differences in the susceptibility of isolates from periodontitis patients or from control individuals.

A new imidazole alkaloid and other constituents from Pilocarpus grandiflorus and their antifungal activity

The stems of Pilocarpus grandiflorus have afforded the new imidazole alkaloid 4,6-dehydro-1,2,4,5-tetrahydro-2,5-dioxopilocarpine in addition to the 17 known compounds germanicol, β-amiryn, ocotillone, stigmast-4-en-3-one, 3β-hydroxy-stigmast-5-en-7-one, 6β-hydroxy-stigmast-4-en-3-one, β-sitosterol, scopoletin, 3-(1′,1′-dimethylallyl)-scopoletin, elisin, dictamine, 4-methoxy-2-quinolone, platydesmine, syringaresinol, syringaldehyde, syringic acid and vanillic acid. Their structures were elucidated on the basis of chemical and spectroscopic evidence. The phenolic compounds vanillic acid and syringaldehyde and the furoquinoline alkaloid platydesmine exhibited antifungal activity against Leucoagaricus gongylophorus, the symbiotic fungus of leaf-cutting ants (Atta sexdens rubropilosa). © 2005 Verlag der Zeitschrift für Naturforschung.

Amphibian secretions for drug discovery studies: A search for new antiparasitic and antifungal compounds

The antiparasitic and antifungal activities of nine amphibian skin secretions were studied in different in vitro models. Seven secretions presented a considerable antiprotozoan activity and one showed promising results against Candida sp. These results can be the basis for the development of new drugs, especially for neglected parasitic diseases. © 2007 Bentham Science Publishers Ltd.

Comparative study of disk diffusion and microdilution methods for evaluation of antifungal activity of natural compounds against medical yeasts Candida spp and Cryptococcus sp

Antifungal activity of natural products has been tested by adapting methods designed for synthetic drugs. In this study, two methods for the determination of antifungal activity of natural products, agar diffusion and broth microdilution, the CLSI reference methods for synthetic drugs, are compared and discussed. The microdilution method was more sensitive. The minimal inhibitory concentrations (MIC) of crude extracts, fractions and pure substances from different species of the plant families Piperaceae, Rubiaceae, Clusiaceae, Fabaceae and Lauraceae, from the Biota project, were determined. Antifungal activities against Candida albicans, C.krusei, C.parapsilosis and Cryptococcus neoformans were produced by several samples.

It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug

Amphotericin B acts through pore formation at the cell membrane after binding to ergosterol is an accepted dogma about the action mechanism of this antifungal, and this sentence is widely found in the literature. But after 60 years of investigation, the action mechanism of Amphotericin B is not fully elucidated. Amphotericin B is a polyene substance that is one of the most effective drugs for the treatment of fungal and parasite infections. As stated above, the first mechanism of action described was pore formation after binding to the ergosterol present in the membrane. But it has also been demonstrated that AmB induces oxidative damage in the cells. Moreover, amphotericin B modulates the immune system, and this activity has been related to the protective effect of the molecule, but also to its toxicity in the host. This review tries to provide a general overview of the main aspects of this molecule, and highlight the multiple effects that this molecule has on both the fungal and host cells. © 2012 Mesa-Arango, Scorzoni and Zaragoza.

Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drugresistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options. © 2013 SGM.

Synthesis, characterization and antifungal activity of quaternary derivatives of chitosan on Aspergillus flavus

Two series of new chitosan derivatives were synthesized by reaction of deacetylated chitosan (CH) with propyl (CH-Propyl) and pentyl (CH-Pentyl) trimethylammonium bromides to obtain derivatives with increasing degrees of substitution (DS). The derivatives were characterized by 1H NMR and potentiometric titration techniques and their antifungal activities on the mycelial growth of Aspergillus flavus were investigated in vitro. The antifungal activities increase with DS and the more substituted derivatives of both series, CH-Propyl and CH-Pentyl, exhibited antifungal activities respectively three and six times higher than those obtained with commercial and deacetylated chitosan. The minimum inhibitory concentrations (MIC) were evaluated at 24, 48 and 72h by varying the polymer concentration from 0.5 to 16g/L and the results showed that the quaternary derivatives inhibited the fungus growth at polymer concentrations four times lower than that obtained with deacetylated chitosan (CH). The chitosans modified with pentyltrimethylammonium bromide exhibited higher activity and results are discussed taking into account the degree of substitution (DS). © 2012 Elsevier GmbH.

Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile

The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2-5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei. © 2013 Scorzoni et al.

Hydrophobic effect of amphiphilic derivatives of chitosan on the antifungal activity against aspergillus flavus and aspergillus parasiticus

Low molecular weight amphiphilic derivatives of chitosan were synthesized, characterized and their antifungal activities against Aspergillus flavus and Aspergillus parasiticus were tested. The derivatives were synthesized using as starting material a deacetylated chitosan sample in a two step process: the reaction with propyltrimethylammonium bromide (Pr), followed by reductive amination with dodecyl aldehyde. Aiming to evaluate the effect of the hydrophobic modification of the derivatives on the antifungal activity against the pathogens, the degree of substitution (DS1) by Pr groups was kept constant and the proportion of dodecyl (Dod) groups was varied from 7 to 29% (DS2). The derivatives were characterized by 1H-NMR and FTIR and their antifungal activities against the pathogens were tested by the radial growth of the colony and minimum inhibitory concentration (MIC) methods. The derivatives substituted with only Pr groups exhibited modest inhibition against A. flavus and A. parasiticus, like that obtained with deacetylated chitosan. Results revealed that the amphiphilic derivatives grafted with Dod groups exhibited increasing inhibition indexes, depending on polymer concentration and hydrophobic content. At 0.6 g/L, all amphiphilic derivatives having from 7.0 to 29% of Dod groups completely inhibited fungal growth and the MIC values were found to decrease from 4.0 g/L for deacetylated chitosan to 0.25-0.50 g/L for the derivatives. These new derivatives open up the possibility of new applications and avenues to develop effective biofungicides based on chitosan. © 2013 by the authors.