RESUMO
Synthetic organic electrosynthesis has grown in the past few decades by achieving many valuable transformations for synthetic chemists. Although electrocatalysis has been popular for improving selectivity and efficiency in a wide variety of energy-related applications, in the last two decades, there has been much interest in electrocatalysis to develop conceptually novel transformations, selective functionalization, and sustainable reactions. This review discusses recent advances in the combination of electrochemistry and homogeneous transition-metal catalysis for organic synthesis. The enabling transformations, synthetic applications, and mechanistic studies are presented alongside advantages as well as future directions to address the challenges of metal-catalyzed electrosynthesis.
Assuntos
Elementos de Transição , Catálise , Técnicas de Química Sintética , Eletroquímica , MetaisRESUMO
Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy.
Assuntos
Ácido Clorogênico , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Caffeic acid (CA) is a polyphenol belonging to the phenylpropanoid family, commonly found in plants and vegetables. It was first identified by Hlasiwetz in 1867 as a breakdown product of caffetannic acid. CA is biosynthesized from the amino acids tyrosine or phenylalanine through specific enzyme-catalyzed reactions. Extensive research since its discovery has revealed various health benefits associated with CA, including its antioxidant, anti-inflammatory, and anticancer properties. These effects are attributed to its ability to modulate several pathways, such as inhibiting NFkB, STAT3, and ERK1/2, thereby reducing inflammatory responses, and activating the Nrf2/ARE pathway to enhance antioxidant cell defenses. The consumption of CA has been linked to a reduced risk of certain cancers, mitigation of chemotherapy and radiotherapy-induced toxicity, and reversal of resistance to first-line chemotherapeutic agents. This suggests that CA could serve as a useful adjunct in cancer treatment. Studies have shown CA to be generally safe, with few adverse effects (such as back pain and headaches) reported. This review collates the latest information from Google Scholar, PubMed, the Phenol-Explorer database, and ClinicalTrials.gov, incorporating a total of 154 articles, to underscore the potential of CA in cancer prevention and overcoming chemoresistance.
Assuntos
Ácidos Cafeicos , Neoplasias , Humanos , Ácidos Cafeicos/uso terapêutico , Ácidos Cafeicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Fungi are a prolific source of bioactive molecules. During the past few decades, many bioactive natural products have been isolated from marine fungi. Chile is a country with 6435 Km of coastline along the Pacific Ocean and houses a unique fungal biodiversity. This review summarizes the field of fungal natural products isolated from Antarctic and Chilean marine environments and their biological activities.
Assuntos
Produtos Biológicos , Chile , Regiões Antárticas , Biodiversidade , FungosRESUMO
Aristotelia chilensis or "maqui" is a tree native to Chile used in the folk medicine of the Mapuche people as an anti-inflammatory agent for the treatment of digestive ailments, fever, and skin lesions. Maqui fruits are black berries which are considered a "superfruit" with notable potential health benefits, promoted to be an antioxidant, cardioprotective, and anti-inflammatory. Maqui leaves contain non-iridoid monoterpene indole alkaloids which have previously been shown to act on nicotinic acetylcholine receptors, potassium channels, and calcium channels. Here, we isolated a new alkaloid from maqui leaves, now called makomakinol, together with the known alkaloids aristoteline, hobartine, and 3-formylindole. Moreover, the polyphenols quercetine, ethyl caffeate, and the terpenes, dihydro-ß-ionone and terpin hydrate, were also obtained. In light of the reported analgesic and anti-nociceptive properties of A. chilensis, in particular a crude mixture of alkaloids containing aristoteline and hobartinol (PMID 21585384), we therefore evaluated the activity of aristoteline and hobartine on NaV1.8, a key NaV isoform involved in nociception, using automated whole-cell patch-clamp electrophysiology. Aristoteline and hobartine both inhibited Nav1.8 with an IC50 of 68 ± 3 µM and 54 ± 1 µM, respectively. Hobartine caused a hyperpolarizing shift of the voltage-dependence of the activation, whereas aristoteline did not change the voltage-dependence of the activation or inactivation. The inhibitory activity of these alkaloids on NaV channels may contribute to the reported analgesic properties of Aristotelia chilensis used by the Mapuche people.
Assuntos
Alcaloides , Elaeocarpaceae , Humanos , Alcaloides/farmacologia , Alcaloides Indólicos , Extratos Vegetais/farmacologia , Analgésicos/farmacologia , Anti-InflamatóriosRESUMO
Drimys winteri J.R. (Winteraceae) produce drimane sesquiterpenoids with activity against Candida yeast. In this work, drimenol, polygodial (1), isotadeonal (2), and a new drimane α,ß-unsaturated 1,4-dialdehyde, named winterdial (4), were purified from barks of D. winteri. The oxidation of drimenol produced the monoaldehyde drimenal (3). These four aldehyde sesquiterpenoids were evaluated against six Candida species isolated from candidemia patients in Chilean hospitals. Results showed that 1 displays fungistatic activity against all yeasts (3.75 to 15.0 µg/mL), but irritant effects on eyes and skin, whereas its non-pungent epimer 2 has fungistatic and fungicide activities at 1.9 and 15.0 µg/mL, respectively. On the other hand, compounds 3 and 4 were less active. Molecular dynamics simulations suggested that compounds 1-4 are capable of binding to the catalytic pocket of lanosterol 14-alpha demethylase with similar binding free energies, thus suggesting a potential mechanism of action through the inhibition of ergosterol synthesis. According to our findings, compound 2 appears as a valuable molecular scaffold to pursue the future development of more potent drugs against candidiasis with fewer side effects than polygodial. These outcomes are significant to broaden the alternatives to treat fungal infections with increasing prevalence worldwide using natural compounds as a primary source for active compounds.
Assuntos
Candidemia , Fungicidas Industriais , Sesquiterpenos , Aldeídos/farmacologia , Candida , Chile , Ergosterol , Humanos , Irritantes , Lanosterol , Sesquiterpenos Policíclicos , Sesquiterpenos/químicaRESUMO
Fungal biotransformation is an attractive synthetic strategy to produce highly specific compounds with chemical functionality in regions of the carbon skeleton that are not easily activated by conventional organic chemistry methods. In this work, Cladosporium antarcticum isolated from sediments of Glacier Collins in Antarctica was used to obtain novel drimane sesquiterpenoids alcohols with activity against Candida yeast from drimendiol and epidrimendiol. These compounds were produced by the high-yield reduction of polygodial and isotadeonal with NaBH4 in methanol. Cladosporium antarcticum produced two major products from drimendiol, identified as 9α-hydroxydrimendiol (1, 41.4 mg, 19.4% yield) and 3ß-hydroxydrimendiol (2, 74.8 mg, 35% yield), whereas the biotransformation of epidrimendiol yielded only one product, 9ß-hydroxyepidrimendiol (3, 86.6 mg, 41.6% yield). The products were purified by column chromatography and their structure elucidated by NMR and MS. The antifungal activity of compounds 1-3 was analyzed against Candida albicans, C. krusei and C. parapsilosis, showing that compound 2 has a MIC lower than 15 µg/mL against the three-pathogenic yeast. In silico studies suggest that a possible mechanism of action for the novel compounds is the inhibition of the enzyme lanosterol 14α-demethylase, affecting the ergosterol synthesis.
Assuntos
Álcoois , Sesquiterpenos , Álcoois/metabolismo , Candida , Antifúngicos/química , Sesquiterpenos/química , Candida albicans , Biotransformação , Testes de Sensibilidade MicrobianaRESUMO
Many fungi are thought to have developed morphological and physiological adaptations to cope with exposure to UV-B radiation, but in most species, such responses and their protective effects have not been explored. Here, we study the adaptive response to UV-B radiation in the widespread, saprotrophic fungus Serpula himantioides, frequently found colonizing coniferous wood in nature. We report the morphological and chemical responses of S. himantioides to controlled intensities of UV-B radiation, under in vitro culture conditions. Ultraviolet radiation induced a decrease in the growth rate of S. himantioides but did not cause gross morphological changes. Instead, we observed accumulation of pigments near the cell wall with increasing intensities of UV-B radiation. Nuclear magnetic resonance (NMR) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) analyses revealed that xerocomic acid was the main pigment present, both before and after UV-B exposure, increasing from 7 mg/liter to 15 mg/liter after exposure. We show that xerocomic acid is a photoprotective metabolite with strong antioxidant abilities, as evidenced by DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt], and oxygen radical absorbance capacity (ORAC) assays. Finally, we assessed the capacity of xerocomic acid as a photoprotective agent on HEK293 cells and observed better photoprotective properties than those of ß-carotene. Xerocomic acid is therefore a promising natural product for development as a UV-protective ingredient in cosmetic and pharmaceutical products.IMPORTANCE Our study shows the morphological and chemical responses of S. himantioides to controlled doses of UV-B radiation under in vitro culture conditions. We found that increased biosynthesis of xerocomic acid was the main strategy adopted by S. himantioides against UV-B radiation. Xerocomic acid showed strong antioxidant and photoprotective abilities, which has not previously been reported. Our results indicate that upon UV-B exposure, S. himantioides decreases its hyphal growth rate and uses this energy instead to increase the biosynthesis of xerocomic acid, which is allocated near the cell wall. This metabolic switch likely allows xerocomic acid to efficiently defend S. himantioides from UV radiation through its antioxidant and photoprotective properties. The findings further suggest that xerocomic acid is a promising candidate for development as a cosmetic ingredient to protect against UV radiation and should therefore be investigated in depth in the near future both in vitro and in vivo.
Assuntos
Brachyspira/metabolismo , Parede Celular/metabolismo , Pigmentos Biológicos/metabolismo , Raios Ultravioleta , Brachyspira/efeitos da radiação , Parede Celular/efeitos da radiação , Células HEK293 , Humanos , Pigmentos Biológicos/efeitos da radiaçãoRESUMO
Palladium(II)-catalyzed C-H carbonylation reactions of methylene C-H bonds in secondary aliphatic amines lead to the formation of trans-disubstituted ß-lactams in excellent yields and selectivities. The generality of the C-H carbonylation process is aided by the action of xantphos-based ligands and is important in securing good yields for the ß-lactam products.
RESUMO
Chemotherapeutic drugs and radiotherapy are fundamental treatments to combat cancer, but, often, the doses in these treatments are restricted by their non-selective toxicities, which affect healthy tissues surrounding tumors. On the other hand, drug resistance is recognized as the main cause of chemotherapeutic treatment failure. Rosmarinic acid (RA) is a polyphenol of the phenylpropanoid family that is widely distributed in plants and vegetables, including medicinal aromatic herbs, consumption of which has demonstrated beneficial activities as antioxidants and anti-inflammatories and reduced the risks of cancers. Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy, mainly due to its scavenger capacity. This review compiles information from 56 articles from Google Scholar, PubMed, and ClinicalTrials.gov aimed at addressing the role of RA as a complementary therapy in cancer treatment.
Assuntos
Cinamatos , Depsídeos , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Ácido Rosmarínico , Depsídeos/farmacologia , Depsídeos/química , Depsídeos/uso terapêutico , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Cinamatos/química , Humanos , Neoplasias/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêuticoRESUMO
Polysaccharides from wood-rooting fungi have attracted attention due to their broad pharmacological properties. Herein, we report the antitumor and immunomodulatory activities of acid polysaccharides isolated from fungi Gloeosoma mirabile. The polysaccharide extracts displayed significant antiproliferative activity against cancer cell lines (MCF-7, HCT-116, U-937) in a dose-dependent manner and induction of IL-6 in macrophage RAW 264.7. Furthermore, flow cytometry analysis showed that high polysaccharide concentrations induced apoptosis by 83% in HL-60 cells. Based on gas chromatography-mass spectrometry (GC-MS) and Fourier transform infra-red (FT-IR) spectroscopy studies, acidic polysaccharides from G. mirabile were mainly composed of arabinose, α-D-galactopyranose and methyl ß-D-galactopyranoside.
RESUMO
We describe the development of efficient benzannulations of siloxy alkynes with pyridinium and isoquinolinium salts. Such reactions are successfully promoted by a stoichiometric amount of silver(I) benzolate under mild reaction conditions. This process proceeds via a formal inverse-electron demand Diels-Alder reaction, followed by fragmentation of the initially produced bicyclic adducts to deliver a range of synthetically useful phenols and naphthols.
RESUMO
Freshwater availability has decreased alarmingly worldwide, with agriculture playing a vital role in this trend. The assessment of the agricultural water footprint (WFagricultural) and virtual water flows (VWF) is fundamental not only in local water resources management and protection, but also in our understanding of the synergies between local water consumption and global markets. Thus, the WFagricultural - broken down into its components (blue, green, and gray) - of the leading 21 crops (grouped in fruit, legumes, cereals, and vegetables), grown in four basins with the most significant agricultural activity in central Chile was determined, estimated in two consecutive years 2017-2018. In addition, due to their great importance in exports, VWFs were assessed, establishing connections according to their origins and destinations. The results show that the green and gray water footprints increased significantly in the south-central basins, while blue water consumption increased in the basins of the central zone, reflecting an evident WFagricultural transition in accord with latitude and climate conditions. Furthermore, VWF showed an annual increase of 44 %, in about 116 destinations, with Asia, Europe, and North America being the preferred destinations, with annual variations of VWFblue- gray associated with increases in exports of apples, cherries, grapes, blueberries, and walnuts, market preferences and growing areas. The present study is an initial step toward sustainable agriculture in a commodity exporting country, one that is relevant in the exploitation of virtual water yet faces severe water deficit problems, distribution, and local water policies. Therefore, contributing to encouraging the efficiency and value of water in the process of a new institutional framework.
RESUMO
Fungal polysaccharides possess a broad biological activity, including cytotoxic and antioxidant activities. This work aimed to evaluate the cytotoxic and antioxidant activity of the acidic polysaccharides of Phylloporia boldo strain (named PBAP40). Cytotoxic activity of polysaccharide was evaluated determining the viability of three tumor cell lines by MTT assay. The effect of acidic polysaccharide on the cell cycle of HL-60 cell line was evaluated by flow cytometry, and the antioxidant activity was determined by DPPH and ABTS assays. PBAP40 showed cytotoxic effects in tumor cell lines. Results suggest that P. boldo acidic polysaccharides arrested tumor cells in the cell cycle Sub G1 phase. The acidic polysaccharides of PBAP40 strain were not cytotoxic for the non-tumor cell line. PBAP40 also showed excellent antioxidant activity. The FT-IR analysis of the acidic polysaccharides indicated the presence of glucans bearing α- and ß- type glycosidic bonds.
Assuntos
Antineoplásicos , Basidiomycota , Antioxidantes/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Linhagem Celular Tumoral , Polissacarídeos/farmacologia , Antineoplásicos/farmacologiaRESUMO
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. One of the hallmarks in AD is amyloid-ß peptide (Aß) accumulation, where the soluble oligomers of Aß (AßOs) are the most toxic species, deteriorating the synaptic function, membrane integrity, and neuronal structures, which ultimately lead to apoptosis. Currently, there are no drugs to arrest AD progression, and current scientific efforts are focused on searching for novel leads to control this disease. Lignans are compounds extracted from conifers and have several medicinal properties. Eudesmin (Eu) is an extractable lignan from the wood of Araucaria araucana, a native tree from Chile. This metabolite has shown a range of biological properties, including the ability to control inflammation and antibacterial effects. OBJECTIVE: In this study, the neuroprotective abilities of Eu on synaptic failure induced by AßOs were analyzed. METHODS: Using neuronal models, PC12 cells, and in silico simulations we evaluated the neuroprotective effect of Eu (30 nM) against the toxicity induced by AßOs. RESULTS: In primary cultures from mouse hippocampus, Eu preserved the synaptic structure against AßOs toxicity, maintaining stable levels of the presynaptic protein SV2 at the same concentration. Eu also averted synapsis failure from the AßOs toxicity by sustaining the frequencies of cytosolic Ca2+ transients. Finally, we found that Eu (30 nM) interacts with the Aß aggregation process inducing a decrease in AßOs toxicity, suggesting an alternative mechanism to explain the neuroprotective activity of Eu. CONCLUSION: We believe that Eu represents a novel lead that reduces the Aß toxicity, opening new research venues for lignans as neuroprotective agents.
Assuntos
Doença de Alzheimer , Lignanas , Fármacos Neuroprotetores , Ratos , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Lignanas/farmacologia , Células PC12 , Fármacos Neuroprotetores/farmacologiaRESUMO
Fungi have a unique metabolic plasticity allowing them to produce a wide range of natural products. Since the discovery of penicillin, an antibiotic of fungal origin, substantial efforts have been devoted globally to search for fungal-derived natural bioactive products. Andean region forests represent one of the few undisturbed ecosystems in the world with little human intervention. While these forests display a rich biological diversity, mycological and chemical studies in these environments have been scarce. This review aims to summarise all the efforts regarding the chemical or bioactivity analyses of Agaricomycetes (Basidiomycota) from southern South America environments. Overall, herein we report a total of 147 fungal species, 21 of them showing chemical characterisation and/or biological activity. In terms of chemical cores, furans, chlorinated phenol derivatives, polyenes, lactones, terpenes and himanimides have been reported. These natural products displayed a range of biological activities including antioxidant, antimicrobial, antifungal, neuroprotective and osteoclast-forming suppressing effects.
RESUMO
Antibiotics are extensively used for growth promotion purposes in intensive aquaculture. In Chile, the use of antibiotics in salmon farming is excessive, approximately 62 times more than is used in Norway. In the salmon industry, antibiotics such as oxytetracycline (OTC) are administered in the diet, both in the juvenile stage in freshwater and in the fattening process of salmon in marine sectors. We have investigated the fjords of Chile, where many salmon farms are located, searching for fungi able to degrade this tetracycline antibiotic. We have evaluated the OTC degradation ability of the following; Penicillium commune, Epicoccum nigrum, Trichoderma harzianum, Aspergillus terreus and Beauveria bassiana, isolated from sediments in salmon farms from southern Chile. In all these fungal strains, the amount of OTC decreased in the culture medium, as adsorbed in the mycelia, after the third day of exposure. These strains were capable of degrading OTC at remarkable rates up to 78%, by the 15th day. This is the first study showing that the mycelium of these fungal strains has the ability to degrade OTC. We believe the knowledge produced by these results has the potential to serve as a basis for implementing a bioremediation process in the near future.
Assuntos
Antibacterianos/metabolismo , Biodegradação Ambiental , Sedimentos Geológicos/microbiologia , Micélio/metabolismo , Oxitetraciclina/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Chile , Pesqueiros , Fungos/metabolismo , SalmãoRESUMO
Phylogenetic relationships of 12 species in Aleurodiscus sensu lato (Stereaceae, Russulales) described from the Patagonian forests of Chile and Argentina were investigated based on sequences of nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and the D1-D2 domains of nuc 28S rDNA (28S). A new genus and a new species are presented, and 10 new combinations proposed. The genus Gloeosoma is shown to be phylogenetically well supported and morphologically circumscribed; it includes G. vitellinum (type species), G. mirabile, comb. nov., G. zealandicum, comb. nov., and Gloeosoma decorticans, sp. nov., which is newly described from Chile. The new genus Stereodiscus is proposed to accommodate a group of taxa characterized by an austral distribution and morphologically by smooth, thin-walled, amyloid basidiospores and a lack of gloeocystidia and acanthocystidia; three species develop Stereum-like basidiomata and two species present discoid ones. The new genus includes the species formerly known as Aleurodiscus antarcticus, A. limonisporus, A. parmuliformis, A. patagonicus, and A. triviale. Specimens of Stereodiscus parmuliformis (A. parmuliformis) from New Zealand (where it was originally described) and southern Chile are shown to be phylogenetically conspecific, which confirms its presence in Patagonia. Gloeosoma and Stereodiscus are shown to be distantly related to Aleurodiscus s. str. and other genera in Stereaceae. The new combinations Aleurocystidiellum bernicchiae, Aleurocystidiellum hallenbergii, and Acanthobasidium quilae are proposed based on morphology and phylogenetic analyses, and Aleurodiscus cerussatus is shown to be a cryptic species complex.
Assuntos
Besouros , Animais , Besouros/genética , DNA Fúngico/genética , DNA Ribossômico/genética , DNA Espaçador Ribossômico/genética , Filogenia , Análise de Sequência de DNARESUMO
The development of electrochemical catalytic conversion of 5-hydroxymethylfurfural (HMF) has recently gained attention as a potentially scalable approach for both oxidation and reduction processes yielding value-added products. While the possibility of electrocatalytic HMF transformations has been demonstrated, this growing research area is in its initial stages. Additionally, its practical applications remain limited due to low catalytic activity and product selectivity. Understanding the catalytic processes and design of electrocatalysts are important in achieving a selective and complete conversion into the desired highly valuable products. In this Minireview, an overview of the most recent status, advances, and challenges of oxidation and reduction processes of HMF was provided. Discussion and summary of voltammetric studies and important reaction factors (e. g., catalyst type, electrode material) were included. Finally, biocatalysts (e. g., enzymes, whole cells) were introduced for HMF modification, and future opportunities to combine biocatalysts with electrochemical methods for the production of high-value chemicals from HMF were discussed.
RESUMO
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder that slowly destroys memory. The precise mechanism of AD is still not entirely understood and remains under discussion; it is believed to be a multifactorial disease in which a number of mechanisms are involved in its pathogenesis. Worldwide, near 37 million people suffer from the effects of AD. As a cause of death for elderly, it is predicted that AD will rank third in the coming years, just behind cancer and heart disease. Unfortunately, AD remains an incurable condition. Despite the devastating problems associated with AD, there are only four FDA approved drugs for palliative treatment of this pathology. Hence, renewed scientific efforts are required not only to uncover more insights into the AD process but also to develop more efficient pharmacological tools against this disease. Due to the complexity and multiple mechanisms at play in the progression of AD, the development of drugs by rational design is extremely difficult. The existing drugs to fight against Alzheimer's have had limited success, mainly due to their ability to modulate only one of the mechanisms involved in AD. As opposed to single-targeted strategies, the identification of small molecules able to affect multiple pathways involved in Alzheimer's is a promising strategy to develop more efficient medicines against this disease. Central to existing efforts to develop pharmaceuticals controlling AD is the discovery of new chemicals displaying strong neuroactivity. Benzofurans are privileged oxygen containing heterocycles that have a strong neuroprotective behavior, inhibiting several of the important events involved in the AD process. In this review, an approach is presented that relies on expanding the neuroprotective chemical space of benzofuran scaffolds by accessing them from Andean-Patagonian fungi and synthetic sources (chemical libraries). The exploration of the neuroprotective chemical space of these scaffolds has the potential to allow the discovery of substitution patterns that display multi-target neuroactivity against multiple events involved in AD. This benzofuran chemical framework will establish a multi-target chemical space that could set the basis for the development of super drugs against AD.