Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi

Many compounds produced by fungi have relevant pharmaceutical applications. The purpose of this study was to collect and isolate endophytic fungi from different regions of Panama and then to test their potential therapeutic activities against Leishmania donovani, Plasmodium falciparum, and Trypanosoma cruzi as well as their anticancer activities in MCF-7 cells. Of the 25 fungal isolates obtained, ten of them had good anti-parasitic potential, showing selective activity against L. donovani; four had significant anti-malarial activity; and three inhibited the growth of T. cruzi. Anticancer activity was demonstrated in four isolates. Of the active isolates, Edenia sp. strain F0755, Xylaria sp. strain F1220, Aspergillus sp. strain F1544, Mycoleptodiscus sp. strain F0194, Phomopsis sp. strain F1566, Pycnoporus sp. strain F0305, and Diaporthe sp. strain F1647 showed the most promise based on their selective bioactivity and lack of toxicity in the assays.Many compounds produced by fungi have relevant pharmaceutical applications. The purpose of this study was to collect and isolate endophytic fungi from different regions of Panama and then to test their potential therapeutic activities against Leishmania donovani, Plasmodium falciparum, and Trypanosoma cruzi as well as their anticancer activities in MCF-7 cells. Of the 25 fungal isolates obtained, ten of them had good anti-parasitic potential, showing selective activity against L. donovani; four had significant anti-malarial activity; and three inhibited the growth of T. cruzi. Anticancer activity was demonstrated in four isolates. Of the active isolates, Edenia sp. strain F0755, Xylaria sp. strain F1220, Aspergillus sp. strain F1544, Mycoleptodiscus sp. strain F0194, Phomopsis sp. strain F1566, Pycnoporus sp. strain F0305, and Diaporthe sp. strain F1647 showed the most promise based on their selective bioactivity and lack of toxicity in the assays

Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi

Parasitic infections are major causes of human chronic diseases in most countries of the tropics. The parasites include protozoa and helminths, infect billions of people, and the resulting diseases cause debilitating injuries such as blind ness and disfigurement, or death in millions of people. According to World Health Organization (WHO) estimates, 25% of the human population is infected with parasitic worms. However, attempts to develop vaccines against these pathogens have been frustrated by the difficulty of cultivating the parasites in the laboratory, the complexity of their multicellular organization and—in many species—their multistage development, in addition to their impressive antigenic variability [http://www.who.int/vaccine_research/diseases/ soa_parasitic/en/index.html]. Malaria is the most dangerous parasitic disease, as evidenced by the high rates of complications and mortality caused by the most fatal species, Plasmodium falciparum [15]. Chagas disease, or American trypanosomiasis, is a potentially life-threatening two-phase illness caused by the protozoan Trypanosoma cruzi. The acute phase persists for about two months after infection; symptoms are absent or mild and can include fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain. In the chronic phase, the parasites reside mainly in the heart and digestive muscle, resulting in cardiac disorders in up to 30% of patients and digestive, neurological, or mixed pathologies in up to 10%. Eventually, the infection can lead to sudden death or heart failure, caused by progressive destruction of cardiac muscle [10,15]. Leishmaniasis, a worldwide disease, is caused by several species of the flagellated protozoan parasite Leishmania. In its more severe forms, the disease causes serious disfigurement and may be fatal. The WHO estimates a worldwide prevalence of leishmaniasis of approximately 12 million cases, with an annual mortality of about 60,000 and approximately 350 million people at risk. The expansion of leishmaniasis and the alarming rise in the number of cases has been attributed to environmental changes, such as deforestation, dam construction, new irrigation schemes, and the migration of non-immune individuals to endemic areas [10,15]. At the same time, the frequency of drug-resistant parasites has greatly increased and most treatments involve highly toxic drugs. In addition, the chemotherapeutic agents used in patients with these diseases have lacked effectiveness. Thus, there is an urgent need to search for novel drugs from previously unexplored sources, including natural products, to combat the global health problems posed by parasitic infections. Cancer is another major cause of mortality worldwide; in 2008, it accounted for 7.6 million deaths. According to WHO forecasts, an increase to 11 million deaths annually is expected by 2030. The prevalence is higher in low and middle-income countries. As a part of the on-going research activities, the Panamanian International Cooperative Biodiversity Group (ICBG) [17] recently decided to explore endophytic fungi as a source of molecules with antiparasitic and anticancer bioactivities [18,21,22]. Within the ICBG program, we have assayed the antiparasitic and in vitro anticancer activities of 25 isolates, while also analyzing the effect of the culture medium on the production of secondary metabolites by Panamanian endophytic fungi. The results of these studies are reported and discussed hereinParasitic infections are major causes of human chronic diseases in most countries of the tropics. The parasites include protozoa and helminths, infect billions of people, and the resulting diseases cause debilitating injuries such as blind ness and disfigurement, or death in millions of people. According to World Health Organization (WHO) estimates, 25% of the human population is infected with parasitic worms. However, attempts to develop vaccines against these pathogens have been frustrated by the difficulty of cultivating the parasites in the laboratory, the complexity of their multicellular organization and—in many species—their multistage development, in addition to their impressive antigenic variability [http://www.who.int/vaccine_research/diseases/ soa_parasitic/en/index.html]. Malaria is the most dangerous parasitic disease, as evidenced by the high rates of complications and mortality caused by the most fatal species, Plasmodium falciparum [15]. Chagas disease, or American trypanosomiasis, is a potentially life-threatening two-phase illness caused by the protozoan Trypanosoma cruzi. The acute phase persists for about two months after infection; symptoms are absent or mild and can include fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain. In the chronic phase, the parasites reside mainly in the heart and digestive muscle, resulting in cardiac disorders in up to 30% of patients and digestive, neurological, or mixed pathologies in up to 10%. Eventually, the infection can lead to sudden death or heart failure, caused by progressive destruction of cardiac muscle [10,15]. Leishmaniasis, a worldwide disease, is caused by several species of the flagellated protozoan parasite Leishmania. In its more severe forms, the disease causes serious disfigurement and may be fatal. The WHO estimates a worldwide prevalence of leishmaniasis of approximately 12 million cases, with an annual mortality of about 60,000 and approximately 350 million people at risk. The expansion of leishmaniasis and the alarming rise in the number of cases has been attributed to environmental changes, such as deforestation, dam construction, new irrigation schemes, and the migration of non-immune individuals to endemic areas [10,15]. At the same time, the frequency of drug-resistant parasites has greatly increased and most treatments involve highly toxic drugs. In addition, the chemotherapeutic agents used in patients with these diseases have lacked effectiveness. Thus, there is an urgent need to search for novel drugs from previously unexplored sources, including natural products, to combat the global health problems posed by parasitic infections. Cancer is another major cause of mortality worldwide; in 2008, it accounted for 7.6 million deaths. According to WHO forecasts, an increase to 11 million deaths annually is expected by 2030. The prevalence is higher in low and middle-income countries. As a part of the on-going research activities, the Panamanian International Cooperative Biodiversity Group (ICBG) [17] recently decided to explore endophytic fungi as a source of molecules with antiparasitic and anticancer bioactivities [18,21,22]. Within the ICBG program, we have assayed the antiparasitic and in vitro anticancer activities of 25 isolates, while also analyzing the effect of the culture medium on the production of secondary metabolites by Panamanian endophytic fungi. The results of these studies are reported and discussed herei

Domestication Syndrome in Caimito (Chrysophyllum cainito L.): Fruit and Seed Characteristics

Domestication Syndrome in Caimito (Chrysophyllum cainitoL.): Fruit and Seed Characteristics: The process of domestication is understudied and poorly known for many tropical fruit tree crops. The star apple or caimito tree (Chrysophyllum cainito L., Sapotaceae) is cultivated throughout the New World tropics for its edible fruits. We studied this species in central Panama, where it grows wild in tropical moist forests and is also commonly cultivated in backyard gardens. Using fruits collected over two harvest seasons, we tested the hypothesis that cultivated individuals of C. cainito show distinctive fruit and seed characteristics associated with domestication relative to wild types. We found that cultivated fruits were significantly and substantially larger and allocated more to pulp and less to exocarp than wild fruits. The pulp of cultivated fruits was less acidic; also, the pulp had lower concentrations of phenolics and higher concentrations of sugar. The seeds were larger and more numerous and were less defended with phenolics in cultivated than in wild fruits. Discriminant Analysis showed that, among the many significant differences, fruit size and sugar concentration drove the great majority of the variance distinguishing wild from cultivated classes. Variance of pulp phenolics among individuals was significantly higher among wild trees than among cultivated trees, while variance of fruit mass and seed number was significantly higher among cultivated trees. Most traits showed strong correlations between years. Overall, we found a clear signature of a domestication syndrome in the fruits of cultivated caimito in Panama

Lentinoids A–D, New Natural Products Isolated from Lentinus strigellus

Four novel lentinoids (1–4), along with the known compounds striguellone A (5), isopanepoxydone (6) and panepoxydone (7), were isolated as part of our studies on Lentinus strigellus. The structures of 1–4 have been established by 1D- and 2D-NMR and MS analysis. Compounds (1–3) and (5–7) were tested against Listeria monocytogenes, Enterococcus faecalis, Pseudomonas aeruginosa and Klebsiella pneumoniae. These compounds showed inhibition diameters ranging from 7.5–9.5 mm, however, when the minimum inhibitory concentration (MIC) was determined, only compound 1 showed a significant activity of 200 μg/mL. Intermediates for the biosynthesis of the oxygenated cyclohexenyl derivatives isolated from lentinoid fungi (genera Lentinus and Panus) are proposed

Structurally Uncommon Secondary Metabolites Derived from Endophytic Fungi

Among microorganisms, endophytic fungi are the least studied, but they have attracted attention due to their high biological diversity and ability to produce novel and bioactive secondary metabolites to protect their host plant against biotic and abiotic stress. These compounds belong to different structural classes, such as alkaloids, peptides, terpenoids, polyketides, and steroids, which could present significant biological activities that are useful for pharmacological or medical applications. Recent reviews on endophytic fungi have mainly focused on the production of novel bioactive compounds. Here, we focus on compounds produced by endophytic fungi, reported with uncommon bioactive structures, establishing the neighbor net and diversity of endophytic fungi. The review includes compounds published from January 2015 to December 2020 that were catalogued as unprecedented, rare, uncommon, or possessing novel structural skeletons from more than 39 different genera, with Aspergillus and Penicillium being the most mentioned. They were reported as displaying cytotoxic, antitumor, antimicrobial, antiviral, or anti-inflammatory activity. The solid culture, using rice as a carbon source, was the most common medium utilized in the fermentation process when this type of compound was isolated

Two Genera of Aulacoscelinae Beetles Reflexively Bleed Azoxyglycosides Found in Their Host Cycads

Aulacoscelinae beetles have an ancient relationship with cycads (Cycadophyta: Zamiaceae), which contain highly toxic azoxyglycoside (AZG) compounds. How these “primitive” leaf beetles deal with such hostderived compounds remains largely unknown. Collections were made of adult Aulacoscelis appendiculata from Zamia cf. elegantissima in Panama, A. vogti from Dioon edule in Mexico, and Janbechynea paradoxa from Zamia boliviana in Bolivia. [...] Nuclear magnetic resonance and mass spectroscopy identified two AZGs, cycasin and macrozamin, in the reflex bleeding; this is the first account of potentially plant-derived compounds in secretions of the Aulacoscelinae. These data as well as the basal phylogenetic position of the Aulacoscelinae suggest that sequestration of plant secondary metabolites appeared early in leaf beetle evolution

Identification of Secondary Metabolites from the Mangrove-Endophyte <i>Lasiodiplodia iranensis</i> F0619 by UPLC-ESI-MS/MS

Lasiodiplodia is a widely distributed fungal genus, frequently found in tropical and subtropical regions where it can cause disease in important crops. It represents a promising source of active secondary metabolites with uses in chemical, pharmaceutical, and agrochemical processes. In this study, the strain Lasiodiplodia iranensis F0619 was isolated from the mangrove Avicennia ger-minans, collected from Sarigua National Park in the Republic of Panama. Fractions of crude extract were analyzed by UPLC-ESI-MS/MS, and five compounds, previously reported from Lasiodiplodia genus were identified, including 11,12-didehydro-7-iso-jasmonic acid (1), 4,5-didehydro-7-iso-jasmonic acid (2), cyclo-(L-Leu-L-Pro) (3), jasmonate-threonine (4), and abscisic acid (5). We describe and analyze their MS/MS fragmentation patterns to confirm the compounds ‘chemical structures