β-Carboline Alkaloids from Galianthe ramosa Inhibit Malate Synthase from Paracoccidioides spp (original) (raw)
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Antimicrobial Agents and Chemotherapy, 2015
Paracoccidioides is the agent of paracoccidioidomycosis. Malate synthase plays a crucial role in the pathogenicity and virulence of various fungi, such as those that are human pathogens. Thus, an inhibitor of this enzyme may be used as a powerful antifungal without side effects in patients once these enzymes are absent in humans. Here, we searched for compounds with inhibitory capacity against the malate synthase of Paracoccidioides species ( Pb MLS). The three-dimensional (3D) structure of Pb MLS was determined using the I-TASSER server. Compounds were selected from the ZINC database. Based on the mechanism underlying the interaction of the compounds with Pb MLS, it was possible to identify β-carboline moiety as a standard key structure. The compounds with β-carboline moiety that are available in our laboratories were investigated. A total of nine alkaloid compounds were selected. The primary mechanisms of interaction of the alkaloid compounds in the binding pocket of Pb MLS were i...
Antimicrobial agents and chemotherapy, 2018
Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the genus, which is restricted to Latin America. The infection is acquired through the inhalation of conidia that primarily lodge in the lungs and may disseminate to other organs and tissues. The treatment for PCM is commonly performed via the administration of antifungals such as amphotericin B, co-trimoxazole, and itraconazole. The antifungal toxicity and side effects, in addition to their long treatment times, have stimulated research for new bioactive compounds. Argentilactone is compound that was isolated from the Brazilian savanna plant , and it has been suggested to be a potent antifungal, inhibiting the dimorphism of and the enzymatic activity of isocitrate lyase, a key enzyme of the glyoxylate cycle. This work was developed due to the importance of elucidating the putative mode of action of argentilactone. The chemoproteomics approach via affinity chromato...
Identification and Mode of Action of a Plant Natural Product Targeting Human Fungal Pathogens
Antimicrobial agents and chemotherapy, 2017
Candida albicans is a major cause of fungal diseases in humans, and its resistance to available drugs is of concern. In an attempt to identify novel antifungal agents, we initiated a small-scale screening of a library of 199 natural plant compounds (i.e., natural products [NPs]). In vitro susceptibility profiling experiments identified 33 NPs with activity against C. albicans (MIC50s ≤ 32 μg/ml). Among the selected NPs, the sterol alkaloid tomatidine was further investigated. Tomatidine originates from the tomato (Solanum lycopersicum) and exhibited high levels of fungistatic activity against Candida species (MIC50s ≤ 1 μg/ml) but no cytotoxicity against mammalian cells. Genome-wide transcriptional analysis of tomatidine-treated C. albicans cells revealed a major alteration (upregulation) in the expression of ergosterol genes, suggesting that the ergosterol pathway is targeted by this NP. Consistent with this transcriptional response, analysis of the sterol content of tomatidine-tre...
Scientia Pharmaceutica
The species of the genus Tabernaemontana have a long tradition of use in different pathologies of infectious origins; the antibacterial, antifungal, and antiviral effects related to the control of the pathologies where the species of this genus are used, have been attributed to the indole monoterpene alkaloids, mainly those of the iboga type. There are more than 1000 alkaloids isolated from different species of Tabernaemontana and other genera of the Apocynaceae family, several of which lack studies related to antibacterial activity. In the present study, four monoterpene indole alkaloids were isolated from the seeds of the species Tabernaemontana cymosa Jacq, namely voacangine (1), voacangine-7-hydroxyindolenine (2), 3-oxovoacangine (3), and rupicoline (4), which were tested in an in vitro antibacterial activity study against the bacteria S. aureus, sensitive and resistant to methicillin, and classified by the World Health Organization as critical for the investigation of new antib...
Indole alkaloids: 2012 until now, highlighting the new chemical structures and biological activities
Fitoterapia, 2020
Indole alkaloids have attracted attention because of their therapeutic properties, being anti-inflammatory, antinociceptive, antitumoural, antioxidant and antimicrobial. These compounds present a wide structural diversity, which is directly related to the genera of the producing plants, as well as the biological activities. Indole alkaloids have attracted attention over the last decade because of this combination of bioactivity and structural diversity. Therefore, this review presented recent (2012-2018) advances in alkaloids, focusing on new compounds, extraction methods and biological activities. As such, approximately 70 articles were identified, which showed 261 new compounds produced by plants of the families Apocynaceae, Rubiaceae, Annonaceae and Loganiaceae. In addition, different extraction methods were identified, and the structures of the new compounds were analysed. In addition to indole molecules, there were mono-indole-, di-indole-, vinblastine-, vimblastine-, gelsedine-, geissospermidine-, koumine-, geissospermidine-, iboga-, perakine-, corynanthe-, vincamine-, ajmaline-, aspidorpema-, strychnos-type, β-carboline alkaloids and indole alkaloid glucosides. The reported biological activities are mainly anticancer, antibacterial, antimalarial, antifungal, antiparasitic, and antiviral, as well as anti-acetylcholinesterase and anti-butyrylcolinesterase properties. This review serves as a guide for those wishing to find the most recently identified alkaloid structures and their associated activities.
Natural products – antifungal agents derived from plants
Journal of Asian Natural Products Research, 2009
A new spectrum of human fungal infections is increasing due to increased cancer, AIDS, and immunocompromised patients. The increased use of antifungal agents also resulted in the development of resistance to the present drugs. It makes necessary to discover new classes of antifungal compounds to cure fungal infections. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, saponins, alkaloids, flavonoids, and other compounds, reported to have in vitro antifungal properties. Since the plant kingdom provides a useful source of lead compounds of novel structure, a wide-scale investigation of species from the tropics has been considered. Therefore, the research on natural products and compounds derived from natural products has accelerated in recent years due to their importance in drug discovery. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans. These molecules may be used directly or considered as a precursor for developing better molecules. This review attempts to summarize the current status of important antifungal compounds from plants.
9. Natural products: Anti-fungal agents derived from plants
As new spectrums of human fungal infections are increasing due to increased cancer and AIDS patients. The increased use of antifungal agents also resulted in the development of resistance to these drugs. It makes necessary to discover new classes of antifungal compounds to treat fungal infections. The research on natural products and natural products derived compounds has accelerated in recent years due to their importance in drug discovery. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, alkaloids, and flavonoids, reported to have in vitro antifungal properties. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans and plants. These molecules may be used directly or considered as a model for developing better molecules. This review attempts to summarize the current status of reported antifungal compounds from plants.
Biocatalysis and agricultural biotechnology, 2019
The medical importance of invasive fungal diseases (IFD) contrasts with the limited therapeutic arsenal available and the increasing resistance rate of pathogenic fungi. Thus, the search for news antifungal drugs is imperative. Many studies highlight the antimicrobial activity of plants from Lamiaceae family such as Melissa officinalis, Mentha sp., Ocimum basilicum, Plectranthus barbatus and Rosmarinus officinalis, but the antifungal potential these species remains still poorly known. The present study was to evaluate the effect of these Lamiaceae species against fungi involved in IFDs. Fresh plants were macerated with ethanol and the extract obtained was partitioned with different solvents. Phytochemical analyzes were conducted and the volatile compounds were investigated by gas chromatography/mass spectrometry (GC/MS). Subsequently, the standardized vegetal material was used to evaluate the antifungal activity through minimum inhibitory concentration (MIC) determination. Ethanol extract of M. officinalis, Mentha sp., O. basilicum, and R. officinalis showed good to moderate activity against Paracoccidioides spp. (MIC 62.5-500 μg/mL). The spectrum of antifungal activity of P. barbatus ethanol extract includes, besides P. brasiliensis (MIC 125-500 μg/mL), several species of Candida spp. (MIC 31.25-500 μg/mL) and the yeasts Cryptococcus gattii, Saccharomyces cerevisiae and Rhodotorula mucilaginosa (MIC 62.5 μg/mL). Flavonoids, steroids/triterpenes, and alkaloids were associated with antifungal activity of extracts and fractions, and the phytol was pointed as the main active compound of the extracts. Lamiaceae plants are a promising source of new antifungal prototypes and phytotherapeutic agents for the pharmaceutical industry, especially against Paracoccidioides spp.