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NMR Spectroscopic Data of Mycoleptodiscins A (1) and B (2) (CD 3 OD; 1 H, 600 MHz; 13 C, 150 MHz)
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Two novel reddish-orange alkaloids, mycolep-todiscin A (1) and mycoleptodiscin B (2), were isolated from liquid cultures of the endophytic fungus Mycoleptodiscus sp. that had been isolated from Desmotes incomparabilis in Panama. Elucidation of their structures was accomplished using 1D and 2D NMR spectroscopy in combination with IR spectroscopic an...
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... From the Desmotes incomparabilis leaf tissues isolated an endophytic fungus under Mycoleptodiscus sp. produces Mycoleptodiscus B, which has cancer-preventing action on the prostate, lung and skin cancer cell lines A2508, IMR-90, PC-3, H460 and H522-T1, with IC50 values of 0.780, 0.4, 1 0.600, 0.660 and 0.630 µM (Ortega et al., 2013). ...
Endophytes are endosymbiotic microorganisms colonizing the internal tissues of healthy host plants [1] and possess the ability to improve the quality and growth rate of theirrespective hosts [2]. Their colonization does not produce any disease symptoms or morphological changes like gall formation of plant tissues [3]. Most of the plants on earth arehost to one or more types of endophytes [4]. These endophytes can be either bacteria or fungi [5,6]. Their population density in a host plant can vary from hundreds to more than 9 x 109 bacteria per gram of plant tissue [7,8, 9]. They can be either obligate or a facultative and the obligate types cannot be cultured due to their specificity of growth conditions. On the other hand, facultative endophytes can be cultured outside the plant tissue using artificial nutrient media [10, 11]. Endophytes form an important part of the micro-ecosystem inside plant tissues [12]. The most explored endophytes are non-pathogenic fungi that provide a number of useful characteristics to their host plant. However, bacterial endophytes remain an unexplored group [13]. Any bacteria which could be isolated from a surface-sterilized plant or extracted from its tissues can be called an endophyte if it does not affect the plant negatively. Bacteria can positively promote plant growth whereas studies show that plants are able to select these beneficial bacterial members in their microbiome including those inside the plant tissues [14, 15, 16]. There is no shred of evidence suggesting that these bacteria take advantage in this relationship [17], but certainly, they get protection from pathogens in adverse times. They could also communicate much better than the rhizospheric bacteria at times of stress [18,19]
... Associated with the leaves of Desmotes incomparabilis. PM181110 is a novel depsipeptide isolated from an endophytic fungus Phomopsis glabrae associated with Pongamia pinnata leaves Ortega et al., 2013;Verekar et al., 2014). ...
Endophytes play a vital role in the survival of host plants by aiding defense responses by producing bioactive compounds similar to their host plants. To fulfill the ever-increasing demand for herbal drugs to cure human ailments, researchers are searching for the various sources of bioactive compounds besides medicinal plants. It was reported that in the international market, the demand of 3 kg per year of vinca alkaloids (1.5×106 kg dry leaves are required) to develop powerful plant-derived anticancer drugs. In this regard, this review aims to highlight the endophytes residing in Catharanthus roseus (family: Apocynaceae), capable of synthesizing indole alkaloids, vinblastine, vincristine, vindoline, vinflunine, vincamine, ajmalicine, ajmaline, serpentine, and reserpine used to control cancer, diabetes, malaria, vascular dementia, cardiac diseases, etc. In the search to fulfill the demand, there is urgent need to develop an efficient method of isolation, identification of endophytes, and the down-streaming process for more efficient and sustainable production of vinca alkaloids from endophytic fungus for the cancer treatment products. Microbial fermentation by optimizing media composition, precursors, inducers, and the metabolic bypass inhibitors would be a promising method in the production of vinca alkaloids at industrial scale. Furthermore, different biotechnological strategies such as gene cloning, gene transformation, and mutations can widely be used on endophytic fungi and bacteria in order to increase the productivity of the vinca alkaloids. Thus, advancements in science and technology have increased the extraction yield from vinca alkaloid producing endophytes, thereby improving the overall efficiency of alkaloid production.
... Another previous study has shown mycoleptodiscin B to have moderate cytotoxic properties against four human cancer cell lines (H460, A2058, H522-T1 and PC-3) and IMR-90 cells with IC 50 values ranging from 0.60 to 0.78 mM [6]. Since alkaloids are known to be biologically active and medicinally important for humans as treatment agents in various disease conditions [7e9], this alkaloid, which was recently isolated, was selected for the current study as no in vivo or in silico experiments have been conducted on it to assess the effects it would have on humans. ...
Mycoleptodiscin B is a natural product extracted from the endophytic fungus Mycoleptodiscus sp. found in Sri Lanka and Panama with experimentally unexplored activities for human targets. In this study, a computational methodology was applied to determine druggable targets of mycoleptodiscin B. According to the computational toxicity and pharmacokinetics assessment, mycoleptodiscin B was proven to be a suitable drug candidate. Druggable targets for this compound, aromatase, acidic plasma glycoprotein and androgen receptor, were predicted using reverse docking. A two-step validation of those targets was performed using conventional molecular docking and molecular dynamic (MD) simulations, resulting in aromatase being determined as the potential therapeutic target. Based on molecular mechanics/Generalized Born Surface Area (GBSA) free energies and ligand stability inside the active site cavity during its 120 ns MD run, it can be concluded that mycoleptodiscin B is a potent aromatase inhibitor and could be subjected to further in vitro and in vivo experiments in the drug development pipeline. Consequently, natural product chemists can quickly identify the hidden medicinal properties of their miracle compounds using the computational approach applied in this research.
... Although Mycoleptodiscus species have been widely reported as plant pathogens, some have been isolated as endophytes from Chamaecyparis thyoides (Bills & Polishook 1992a, b), the aquatic Myriophyllum spicatum in the USA (Shearer 2001), Desmotes incomparabilis in Panama (Martínez-Luis et al. 2011, Ortega et al. 2013, Acer truncatum and Cinnamomum camphora in China (Sun et al. 2011, He et al. 2012, Borreria verticillata and Opuntia ficus-indica in Brazil (Andrioli et al. 2012, and Freycinetia sp. in Thailand (Tibpromma et al. 2018). Mycoleptodiscus terrestris has also been isolated as an endophyte from aquatic submersed macrophytes in New Zealand (Hofstra et al. 2009(Hofstra et al. , 2012. ...
Mycoleptodiscus includes plant pathogens, animal opportunists, saprobic and endophytic fungi. The present study presents the first molecular phylogeny and revision of the genus based on four loci, including ITS, LSU, rpb2, and tef1. An extensive collection of Mycoleptodiscus cultures, including ex-type strains from the CBS, IMI, MUCL, BRIP, clinical isolates from the USA, and fresh isolates from Brazil and Spain, was studied morphologically and phylogenetically to resolve their taxonomy. The study showed that Mycoleptodiscus sensu lato is polyphyletic. Phylogenetic analysis places Mycoleptodiscus in Muyocopronales (Dothideomycetes), together with Arxiella, Leptodiscella, Muyocopron, Neocochlearomyces, and Paramycoleptodiscus. Mycoleptodiscus terrestris, the type species, and M. sphaericus are reduced to synonyms, and one new species is introduced, M. suttonii. Mycoleptodiscus atromaculans, M. coloratus, M. freycinetiae, M. geniculatus, M. indicus, M. lateralis (including M. unilateralis and M. variabilis as its synonyms) and M. taiwanensis belong to Muyocopron (Muyocopronales, Dothideomycetes), and M. affinis, and M. lunatus to Omnidemptus (Magnaporthales, Sordariomycetes). Based on phylogenetic analyses we propose Muyocopron alcornii sp. nov., a fungus associated with leaf spots on Epidendrum sp. (Orchidaceae) in Australia, Muyocopron zamiae sp. nov. associated with leaf spots on Zamia (Zamiaceae) in the USA, and Omnidemptus graminis sp. nov. isolated from a grass (Poaceae) in Spain. Furthermore, Neomycoleptodiscus venezuelense gen. & sp. nov. is introduced for a genus similar to Mycoleptodiscus in Muyocopronaceae.
... obtained from leaves of Desmotes incomparabilis. Mycoleptodiscin B when tested against H460, A2058, H522-T1, PC-3 and IMR-90 displayed IC50 values of 0.660, 0.780, 0.630, 0.600, 0.41 µM [17]. ...
Background: The search for natural bioactive metabolites having
potential anticancer property dates back to the Ebers papyrus written in 1550 BC.
Natural products from medicinal plants and microorganisms are the most consistent
and productive source for the “first-in-class” drugs. After two decades of research, a
great deal of interest has been generated by discovery of remarkable
pharmacological agents from endophytic fungi residing asymptomatically within
plant tissues.
Objective: This review substantially covers the novel cytotoxic compounds isolated
from endophytic fungi associated with terrestrial and mangrove plants as well as
other microorganisms such as lichens, during 2011-2015. These natural compounds are described based
on their cytotoxic activity profiles, chemical nature and potential structure–activity relationship deduced
from the biochemical and cytotoxic studies. The anti-cancerous activities of the compounds discussed in
this review are taken from the published reports exhibiting activity against specific cancer cell lines
along with the mechanism of action. These compounds are exclusively isolated from endophytic fungi.
Conclusion: Endophytic fungi can be exploited for isolation of new reliable, economical and
environmentally safe natural bioactive molecules having wide range of applications in agriculture,
medicine and food industry. Over the past few decades much progress has been achieved though, still
many issues such as optimizing the fermentation culture conditions for increasing the compound yield,
elucidating biosynthetic pathway of the compounds in the endophytic fungi needs to be further clarified
and resolved.
... Endophytes are ubiquitous and have been found in all species of plants, and also have been demonstrated to produce large amounts of secondary metabolites (Kharwar et al., 2011). The metabolites exhibited extensive biological activities such as promoting the growth of host plants, improving the plant's ability to tolerate abiotic stresses and enhancing resistance to insects and plant pathogens, and possessed diverse pharmacological activities including cytotoxic, antimicrobial, and anti-inflammatory activities (Liu et al., 2016a;Ortega et al., 2013;Ratnaweera et al., 2015;Zhao et al., 2011). ...
Two new compounds, named leptospyranonaphthazarin A (1) and leptosnaphthoic acid A (2), together with four known compounds (3–6) were isolated from an endophytic fungus Leptosphaerulina sp. SKS032. Their structures were assigned using spectroscopic methods, computational methods, and single-crystal X-ray diffraction analysis. In the antibiotic assay, compounds 1, 2, and 6 exhibited antibacterial activities against Staphylococcus aureus with minimal inhibitory concentration (MIC) values of 25.0, 50.0, and 50.0 μg/mL, respectively.
... Endophytes are ubiquitous and have been found in all species of plants, and also have been demonstrated to produce large amounts of secondary metabolites (Kharwar et al., 2011). The metabolites exhibited extensive biological activities such as promoting the growth of host plants, improving the plant's ability to tolerate abiotic stresses and enhancing resistance to insects and plant pathogens, and possessed diverse pharmacological activities including cytotoxic, antimicrobial, and anti-inflammatory activities (Liu et al., 2016a;Ortega et al., 2013;Ratnaweera et al., 2015;Zhao et al., 2011). ...
Seven new compounds: diaporchromanones A–D (1–4), (−)-phomopsichin A (5a), (+)-phomopsichin B (6a), and (±)-diaporchromone A (7), along with the known (+)-phomopsichin A (5b) and (−)-phomopsichin B (6b) were isolated from an endophytic fungus Diaporthe phaseolorum SKS019. The structures of the new compounds, including their absolute configurations, were determined on the basis of HRESIMS and NMR spectroscopic data, and experimental ECD and Rh2(OCOCF3)4-induced CD spectra analyses. Diaporchromanone A (1)/B (2), and C (3)/D (4) are two pairs of 3-epimers, and their structures possessing 3-substituted-chroman-4-one skeleton are rarely found in natural sources. (−)-Phomopsichin A (5a) and (+)-phomopsichin B (6a) are enantiomers of (+)-phomopsichin A (5b) and (−)-phomopsichin B (6b), respectively. All of the isolates were evaluated for their inhibitory effects against osteoclastogenesis in the RAW 264.7 cell line using luciferase reporter gene assays. Compounds 3–6b exhibited moderate inhibitory effects on osteoclastogenesis by suppressing the receptor activator of NF-κB by ligand-induced NF-κB activation.
... In 2013 two new alkaloids, Mycoleptodiscins A (15) and B (16), with naturally uncommon indol-terpene scaffold were identified from endophytic fungus isolated from Desmotes incomparabilis identified as Mycoleptodiscus sp. (Ortega et al., 2013). ...
Dark septate endophytes (DSE) constitute a very heterogeneous group of Ascomycetes characterized by a septate and melanized mycelium. Inside, tissues show intra- and intercellular development and are able not only to generate mantle and Hartig net but also to produce typical intracellular structures (microsclerotia), all without causing apparent damage to the plant. DSE were previously thought to be restricted to infertile boreal or alpine habitats, where arbuscular mycorrhizal fungi cannot persist. However, in recent years DSE have been found extensively distributed in polluted areas around the world, supporting a growing body of evidence that points to a prominent ecological role, even when these organisms have not been studied from the physiological role of a host-fungi perspective. It has been hypothesized that DSE dominance as root endophytes might relate to their melanised cell walls, known to play an important function in heavy metal immobilization by sequestration. In addition to the improved nutritional performance associated with mycorrhizal fungi, this capacity provides the plant with an extra feature. Due to the promising role on ecological reforestation of the DSE, further research is needed, including new approaches (molecular, histological and physiological) that will allow to better characterize the relationship between these fungi and plants growing in polluted areas.
... In 2013 two new alkaloids, Mycoleptodiscins A (15) and B (16), with naturally uncommon indol-terpene scaffold were identified from endophytic fungus isolated from Desmotes incomparabilis identified as Mycoleptodiscus sp. (Ortega et al., 2013). ...
Introduction: Researches on endophytic fungi have proven they are a promising source
of biocontrol agents. These organisms are present in the internal healthy plant tissues
during a part or/all of their life cycle without causing apparent harm to their hosts. They
influence greatly the physiological activities of their host plants. Fungal endophytes
enhance their host resistance against abiotic stress, disease, insects and mammalian
herbivores by producing a broad range of fungal metabolites. Indeed several interesting
metabolites isolated from endophytic fungi belong to diverse chemical classes, including:
alkaloids, steroids, flavonoids, terpenoids, quinones and phenols. Since the isolation of
paclitaxel in 1993 from an endophytic fungus of Pacific Yew, fungal endophytes took a
consider attention as alternative source of active compounds produced by their host plants,
however they could be an alternative source of novel natural products for exploitation in
modern medicine, agriculture and industry.
Conclusion: The chapter sets out to present general overview of endophytic fungi and
focus on their occurrence, classification, functions and several classes of their secondary
metabolites. Finally examples are given concerning natural products isolated from fungal
endophytes with potent biological activity.
... In 2013 two new alkaloids, Mycoleptodiscins A (15) and B (16), with naturally uncommon indol-terpene scaffold were identified from endophytic fungus isolated from Desmotes incomparabilis identified as Mycoleptodiscus sp. (Ortega et al., 2013). ...
