Cutaneous Leishmaniasis and Chagas disease are neglected tropical diseases that affect millions worldwide. Despite the high morbidity associated with these infections, current treatments are often highly toxic and are showing diminishing efficacy. Thus, new therapeutic options are urgently needed. In this study, bio-guided assays were conducted on the sawdust of Tabebuia chrysantha ("guayacán") to identify promising bioactive compounds. The ethanolic crude extract, five chromatography fractions, pure isoflavans sativan and vestitol, and a mixture were evaluated in vitro against Leishmania braziliensis and Trypanosoma cruzi. High leishmanicidal and trypanocidal activities were observed in the crude extract, fraction F2 (rich in sativan and vestitol), and the two pure isoflavans. Given the abundance and ease of obtaining the isoflavan mixture, its therapeutic potential was further evaluated in vivo in hamsters infected with L. braziliensis and mice infected with T. cruzi. Remarkably, topical and intraperitoneal administration of the chromatography fraction achieved a 67% clinical cure in hamsters with L. braziliensis infection and a 75% reduction in parasitemia in T. cruzi-infected mice. While the antiparasitic effects of certain flavonoids have been documented, this study is the first to demonstrate the efficacy of isoflavans in animal models for both diseases. The potential efficacy observed against T. cruzi and L. braziliensis, two pathogens with limited treatment options and a significant drawback of the available treatments, highlights the therapeutic potential of this combination of sativan and vestitol, which can be derived from timber industry waste, presenting an abundant and accessible source for further development.

Background: According to the WHO, 12 bacteria cause numerous human infections, including Enterobacteriaceae Klebsiella pneumoniae, and thus represent a public health problem. Microbial resistance is associated with biofilm formation; therefore, it is critical to know the biofilm-inducing potential of various compounds of everyday life. Likewise, the reversibility of biofilms and the modulation of persister cells are important for controlling microbial pathogens. In this work, we investigated the biofilm-inducing effects of xanthones from Garcinia mangostana on Klebsiella pneumoniae. Furthermore, we investigated the reversal effect of 3-methyl-2(5H)-furanone and the formation of persister cells induced by xanthones and their role in modulating the biofilm to the antibiotic gentamicin. Methods: To analyze the biofilm-inducing role of xanthones from Garcinia mangostana, cultures of K. pneumoniae containing duodenal probe pieces were treated with 0.1-0.001 mu M alpha- and gamma-mangostin, and the biofilm levels were measured using spectrophotometry. To determine biofilm reversion, cultures treated with xanthones, or gentamicin were mixed with 3-methyl-2(5H)-furanone or N-butyryl-DL-homoserine lactone. The presence of K. pneumoniae persister cells was determined by applying the compounds to the mature biofilm, and the number of colony-forming units was counted. Results: The xanthones alpha- and gamma-mangostin increased K. pneumoniae biofilm production by 40% with duodenal probes. However, 3-methyl-2(5H)-furanone at 0.001 mu M reversed biofilm formation by up to 60%. Moreover, adding the same to a culture treated with gentamicin reduced the biofilm by 80.5%. This effect was highlighted when 3-methyl-2(5H)-furanone was administered 6 h later than xanthones. At high concentrations of alpha-mangostin, persister K. pneumoniae cells in the biofilm were about 5 - 10 times more abundant than cells, whereas, with gamma-mangostin, they were about 100 times more. Conclusion: Two xanthones, alpha- and gamma-mangostin from G. mangostana, induced biofilm formation in K. pneumoniae and promoted persister cells. However, the biofilm formation was reversed by adding 3-methyl-2(5H)-furanone, and even this effect was achieved with gentamicin. In addition, this compound controlled the persister K. pneumoniae cells promoted by alpha-mangostin. Thus, synthetic, and natural biofilm-inducing compounds could harm human health. Therefore, avoiding these substances and looking for biofilm inhibitors would be a strategy to overcome microbial resistance and recover antibiotics that are no longer used.

BackgroundAccording to WHO, over 12 bacteria cause numerous human infections, including Enterobacteriaceae Klebsiella pneumoniae, thus representing a public health problem. Microbial resistance is associated with forming a biofilm; therefore, it is essential to know the inducing potential of the biofilm inducing potential from several compounds. Additionally, establishing the possible reversibility of the biofilm formation is important to design new control methods. In this work, we studied the effects of Klebsiella pneumoniae caused by natural xanthones from Garcinia mangostana. Moreover, we studied the reversal effect of 3-methyl-2(5H)-furanone and its role in modulating the biofilm to gentamicin.MethodsTo analyze the biofilm-inducing role of xanthones isolated from Garcinia mangostana, cultures of K. pneumoniae containing duodenal probes pieces were treated with 0.1–0.001 mM α- and γ-mangostin and biofilm levels were measured by spectrophotometry. To determine the reversion of the biofilm, cultures treated with xanthones, or gentamicin were mixed with 3-methyl-2(5H)-furanone or N-butyryl-DL-homoserine lactone. Then, applying compounds to the mature biofilm established the presence of K. pneumoniae persister cells, and the number of colony-forming units was counted.ResultsXanthones α- and γ-mangostin increased the biofilm production in K. pneumoniae by 40% on duodenal probes. However, 3-methyl-2(5H)-furanone at 0.001 μΜ reversed biofilm formation by up to 60%. Moreover, adding the same to a culture treated with gentamicin reduced the biofilm-forming activity by 80.5%, transforming an inducing effect into an inhibitory one. This effect was highlighted if 3-methyl-2(5H)-furanone was administered six hours later. At high concentrations of α-mangostin, persistent K. pneumoniae cells in the biofilm were about 5-10 times more abundant than the free cells, while in γ-mangostin, they were about 100 times more.ConclusionTwo G. mangostana xanthones induced biofilm formation in K. pneumoniae and persister cells, mainly by γ-mangostin. However, biofilm formation was reversed with the addition of 3-methyl-2(5H)-furanone, and even this effect was also achieved in gentamicin.Natural inducer biofilm compounds could potentially be hazardous to human health. Thus, avoiding these substances and looking for biofilm inhibitors will be a strategy to overcome microbial resistance and recover antibiotics that are no longer used.

Cutaneous leishmaniasis (CL) is an endemic infection in several countries worldwide. Because of variable response to therapy and frequency of relapses, more effective, safer, and inexpensive treatments are needed. The hederagenin glucoside saponins (SS) and chromane hydrazone (TC2) combined in a 1 : 1 ratio have high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage [1]. In this work, we developed an ointment formulation containing 2% TC2 and 2% SS (w/w) and determined the skin permeation and the absorption but also the acute dermal toxicity by in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy to treat non-complicated CL was evaluated in an observational study in human and canine patients from endemic areas of Colombia. Both TC2 and SS diffused through pig ear skin and traces of TC2 but not SS were detected in the stratum corneum of mice at 6 – 24 hours. Neither TC2 nor SS were detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2 – 2% SS ointment produced a complete long-term clinical cure in 10 patients (4 women and 6 men) and 56 dogs (24 females and 32 males) without adverse effects. All human and canine patients have remained disease-free for the last 24 months. In conclusion, these results support the use of topical therapy as a safer and new first-line local treatment of CL that could be further validated by controlled clinical trials.

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2–2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6–24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2–2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.

Cutaneous leishmaniasis (CL) is an infectious disease endemic of tropical and subtropical countries, for which current pharmacologic treatments have serious drawbacks. Therefore, new and improved medical treatments are required. On the other side, natural products have been a valuable source of bioactive molecules, but unlike other products of natural origin, diterpenoids are molecules with only a few studies as antiparasitic drugs. Continuing our work on syntheses of beyerenes, and focusing on obtaining more compounds with antiparasitic activity, we describe in this work the syntheses and activity of several ent-beyerene and ent-kaurene type of compounds against CL, and also their toxicity. Utilizing classical reactions such as Grignard, Mitsunobu, and Williamson, among others, it was possible to modify rings A and D of ent-beyerenes, specifically C-19 on ring A, and C-15 and C-16 on ring D. A total of 40 new compounds were obtained, 21 of them being active against Leishmania (Viannia) braziliensis with median effective concentration (EC50) values less than 25.0 mu g/mL and of these with EC50 values ranging from 1.8 to 7.1 mu g/mL and Selectivity Index (SI) varying from 1.1 to 5.1. All compounds showed to be highly cytotoxic at concentrations less than 100 mu g/mL, except compound 37 that was cytotoxic at 279.7 mu g/mL and moderately active against L. braziliensis (EC50=33.5 mu g/mL and an SI of 8.4. All active compounds were ent-beyerene type.

Fragmento Desde cuando me senté por primera vez en este auditorio y vi una gran superficie en blanco sobre el estrado, me dije entusiasmado: “¡Esa pared está que pide a gritos un mural!”. Lo mismo me decía cada vez que asistía a las sesiones de la Academia, hasta que, por fin, en agosto del 2003 decidí a dar el primer paso: quiénes podrían ser los personajes que debían figurar. Con la disculpa de que estaba interesado en escribir un Opúsculo histórico de la Medicina Nacional, me dirigí a siete reconocidos académicos historiadores: Efraín Otero, Roberto de Zubiría, José Félix Patiño, Juan Mendoza Vega, Hernando Forero Caballero, Alfonso Vargas Rubiano y Adolfo de Francisco, para que me ilustraran sobre quiénes deberían aparecer en mi escrito. La intención al elevar esa consulta era evitar que una vez pintado el mural se me dijera que la escogencia de los personajes había sido arbitraria. De esa encuesta tomé no solamente los diez nombres con los cuales estaban todos de acuerdo, sino también otros que en mi concepto también merecían figurar. En total fueron 14 los personajes escogidos. Yo añadí otro, no mencionado por ninguno, pero que consideré que no podía estar ausente: el Paciente. Transcurría el tiempo y no me atrevía a embarcarme en el proceso de ejecución de la obra. No me sentía capaz, pues era algo monumental (5 metros de ancho por 2,85 de alto), y yo no había pintado nunca un mural. Acudí a mi maestro Ángel Loockartt y le pregunté si era válido pintar la obra en paneles y luego montarlos sobre la pared. Pintar directamente sobre el muro, trepado en un andamio como se hacía en otras épocas, era para mí un imposible, por mis mermadas condiciones físicas a causa de mi avanzada edad. Yo no era un titán como Miguel Ángel. El maestro Loockartt me dijo que hoy era totalmente válido un mural montable y desmontable, y que podía pintarlo en lienzo sobre bastidores, usando pigmentos al óleo y acrílicos, es decir, una técnica mixta.

Toxicity and poor adherence to treatment that favors the generation of resistance in the Leishmania parasites highlight the need to develop better alternatives. Here, we evaluated the in vitro effectiveness of hydrazone derived from chromanes 2-(2,3-dihydro-4H-1-benzothiopyran-4-ylidene) hydrazide (TC1) and 2-(2,3-dihydro-4H-1-benzopyran-4-ylidene) hydrazide (TC2) and the mixture of triterpene saponin hederagenin-3-O-(3,4-O-diacetyl-ß-D-xylopyranosyl-(1à3)-a-L- rhamnopyranosyl-(1à2)-a-L-arabinofuranoside, hederagenin-3-O-(3,4-O-diacetyl-a-L- arabinopyranosyl-(1à3)-a-L-rhamnopyranosyl-(1à2)-a-L-arabinofuranoside and, hederagenin-3-O-(4-O-acetyl-ß-D-xylopyranosyl-(1à3)-a-L-rhamnopyranosyl-(1à2)-a-L-arabinofuranoside from Sapindus saponaria (SS) on L. braziliensis and L. pifanoi. Mixtures of TC1 or TC2 with saponin were formulated for topical application and the therapeutic effectiveness was evaluated in the model for cutaneous leishmaniasis (CL) in golden hamster. The mode of action of these compounds was tested on various parasite processes and ultrastructural parasite modifications. TC1, TC2 and SS showed moderate cytotoxicity when tested independently but toxicity was improved when tested in combination. The compounds were more active against intracellular Leishmania amastigotes. In vivo studies showed that combinations of TC1 or TC2 with SS in 1:1 ratio (w/w) cured 100% of hamsters with no signs associated with toxicity. The compounds did cause changes in the mitochondrial activity of the parasite with a decrease in ATP levels and depolarization of membrane potential and overproduction of reactive oxygen species; nevertheless, these effects were not related to alterations in membrane permeability. The phagolysosome ultrastructure was also affected impacting the survival of Leishmania but the function of the lysosome nor the pH inside the phagolysosome did not change. Lastly, there was a protease inhibition which was directly related to the decrease in the ability of Leishmania to infect and multiply inside the macrophage. The results suggest that the combination of TC1 and TC2 with SS in a 1:1 ratio is capable of curing CL in hamsters. This effect may be due to the ability of these compounds to affect parasite survival and the ability to infect new cells.

Through bioguided in vitro assays, the leishmanicidal and trypanocidal effects of an ethanol extract, seven fractions, and two pure substances obtained from Clathrotropis brunnea Amshoff sawdust were established. The effectiveness of the two metabolites was confirmed in a hamster model of cutaneous Leishmaniasis by Leishmania braziliensis and in Balb/c mice infected by Trypanosoma cruzi. In vitro, 3,5-dimethoxystilbene was the most active against L. braziliensis amastigotes, with a median lethal concentration (LC50) of 4.18 μg/ml (17.40 μM) and a selectivity index of 3.55, but showed moderate activity for T. cruzi, with a median effective concentration (EC50) value of 27.7 μg/ml (115.36 μM). Flavanone pinostrobin, meanwhile, showed high activity against L. braziliensis, with an EC50 of 13.61 μg/ml (50.39 μM), as well as for T. cruzi, with an EC50 of 18.2 μg/ml (67.38 μM). The animal model assay of cutaneous Leishmaniasis showed that 50% of the hamsters treated with pinostrobin were definitively cured the cutaneous ulcer, and 40% showed an improvement, with a reduction in the size of the of 84–87%. Moreover, Balb/c mice experimentally infected with T. cruzi and treated for 25 days with pinostrobin experienced a reduction in their parasitemia by 71%. These results demonstrate the high potential of C. brunnea Amshoff against cutaneous Leishmaniasis and American trypanosomiasis and indicate the pharmacological potential of waste from the wood industry, which has tons of potentially useful chemicals for the development of new medicines.

Chemical investigation of the aerial parts (except fruits and calixes) of Physalis nicandroides var. attenuata led to the isolation of a series of new labdane-type diterpenoids, including the closely related compounds 1-3, the labdane glucosides 4 and 5, a mixture of the epimeric alcohols 6 and 7, and one labdanetriol, isolated as its tri-O-acetyl derivative 9. In addition, three new withanolides (14-16) and six known compounds were isolated. The structures of these compounds were elucidated by analysis of their spectroscopic data and chemical transformations, and those of compounds 1, 4, and 16 were confirmed by X-ray diffraction analysis of the natural product (1) and of the corresponding acetyl derivatives 4a and 16a. Fourteen of these compounds were assayed for their in vitro inhibitory activity against yeast alpha-glucosidase and acetylcholinesterase enzymes. The results were negative in both cases, except for compound 3a that marginally inhibited the activity of acetylcholinesterase with an IC50 value of 64.4 mu M.

En aves, el eje endocrino Hipotalamo-Pituitaria-Adrenal (HPA) esta involucrado en la secrecion de corticosterona, la principal hormona del estres en este grupo de vertebrados. En condiciones normales, los niveles de corticosterona plasmatica fluctuan dentro de un rango inferior de niveles basales que permiten hacer frente a las demandas energeticas predecibles del ambiente. Por el contrario, en respuesta a perturbaciones, los niveles de corticosterona tipicamente se elevan hasta un rango superior de niveles inducidos por estres que promueven cambios fisiologicos y comportamentales adaptativos destinados a aumentar las probabilidades de supervivencia. La exposicion repetida o prolongada a las perturbaciones puede desencadenar estres cronico, provocando la desregulacion del eje HPA con desajustes en la produccion de corticosterona. El trabajo de investigacion llevado a cabo en esta tesis tuvo por finalidad, en primer lugar, estudiar el efecto de la presencia humana en el medio natural como posible fuente de estres cronico en aves. Para ello, se cuantificaron niveles de corticosterona en pollos de ciguena blanca (Ciconia ciconia) expuestos a diferentes grados de presencia humana y se indujo experimentalmente el mecanismo de auto-inhibicion de la secrecion de corticosterona (i.e., feedback negativo) mediante el tratamiento con dexametasona. Nuestros resultados mostraron diferencias de actividad adrenocortical en ciguenas expuestas a humanos respecto a conespecificos libres de presencia humana al utilizar medidas de corticosterona en pluma (que permiten estimar trayectorias fisiologicas a largo plazo) y pasaron desapercibidas en muestras de sangre (que solo reflejan trayectorias fisiologicas a corto plazo). Los resultados no aportaron evidencias de estres cronico y sugirieron una reducida exposicion a estimulos de estres en areas ligadas a presencia humana. En segundo lugar, esta tesis abordo el mecanismo responsable de la atenuacion asociada a la edad en la respuesta adrenocortical al estres de aves altriciales durante el desarrollo post-natal. Esta atenuacion, que sugiere un patron generalizado en aves, se postula como un mecanismo evolutivamente seleccionado para evitar que las elevaciones de corticosterona pongan en peligro el crecimiento y desarrollo normal del individuo cuando sus habilidades para enfrentarse a las perturbaciones son limitadas. En la actualidad, se han propuesto dos hipotesis potenciales para explicar el mecanismo que subyace a este patron : (i) un progresivo crecimiento y maduracion del eje HPA asociado a la edad (Hipotesis de la Maduracion) o (ii) una atenuacion gradual en la intensidad del feedback negativo del eje HPA (Hipotesis de la Atenuacion del Feedback Negativo). Esta cuestion se abordo induciendo feedback negativo mediante el tratamiento con dexametasona en pollos de ciguena blanca. Los resultados indicaron un efecto positivo de la edad sobre las elevaciones de corticosterona plasmatica en respuesta al estres, pero no sobre el feedback negativo, sugiriendo la maduracion progresiva de los tejidos del eje HPA como el mecanismo proximal responsable de dicha atenuacion. En tercer lugar y, por ultimo, se utilizaron implantes de corticosterona en pollos y adultos de ciguena blanca para cuantificar sus efectos sobre la funcion adrenocortical. Los implantes se utilizan en estudios de endocrinologia evolutiva y del comportamiento como una herramienta util destinada a simular elevaciones cronicas de corticosterona (durante varios dias) y estudiar sus efectos sobre determinados rasgos biologicos. En nuestros experimentos con ciguena blanca, y en contra de nuestras predicciones iniciales, los implantes redujeron los niveles basales e inducidos de corticosterona plasmatica. Una revision de 50 estudios revelo que los niveles basales de corticosterona aumentan generalmente (72% de los experimentos) mientras que los niveles inducidos por estres se reducen (78% de los experimentos) tras el tratamiento con implantes. Los resultados de esta revision pusieron en contexto los resultados hallados en ciguenas y contribuyeron a expandir las asunciones prevalentes en el uso de implantes porque: (i) los niveles basales mostraron una asociacion cuadratica con la dosis del implante de forma general en las aves, y la reduccion de estos niveles ocurrio a dosis altas y bajas, y (ii) los implantes de corticosterona tambien redujeron los niveles inducidos, generando asi fenotipos hipo-responsivos al estres. Esta revision contribuyo ademas a revelar importantes sesgos de estudio en el uso de implantes por investigadores. En resumen, esta tesis estudia el efecto de factores externos e internos al organismo sobre la funcion adrenocortical de las aves, profundiza en conocer los potenciales mecanismos proximales que permiten esa funcion y genera conocimientos practicos de aplicacion para futuros experimentos.

In searching for better therapeutic alternatives to treat cutaneous leishmaniasis (CL), this study aimed to obtain and evaluate the efficacy and toxicity of new chroman-4-one hydrazones derivatives. Compounds were prepared and characterized, and then transformed into hydrazonas for molecular optimization. Their cytotoxicity was tested in different cell types using an in vitro MTT assay and the efficacy was evaluated using an in vitro macrophage intracellular amastigotes of Leishmania (Viannia) panamensis and L. (V) braziliensis by flow cytometry. The therapeutic effect of two formulations of chroman-4-one hydrazones on the CL induced by L. (V) braziliensis in golden hamsters was determined according to the size of lesions after treatment. The effect of these compounds in the production of inflammatory mediators and cell migration was also determined by in vitro assays using human fibroblasts models. Neither cytotoxicity nor genotoxicity was observed. The benzoic acid hydrazone derivative 2-(2,3-dihydro-4H-1-benzopyran-4-ylidene) hydrazide (4), produced a higher percentage of clinical cures, followed by benzoic acid, 2-(2,3-dihydro-4H-1-benzothiopyran-4-ylidene) hydrazide (3), while benzoic acid, 2-(2,3-dihydro-1,1-dioxide-4H-1-benzothiopyran-4-ylidene) hydrazide (5) and 4-pyridinecarboxylic acid, 2-(4H-1-benzopyran-4-ylidene) hydrazide (6) caused a poor therapeutic response. The compound 4 also showed an effect in the inflammatory and fibroblast migration processes. In conclusion, this is the first report of antileishmanial activity combined with inflammatory and wound healing properties. Results obtained here suggest that this strategy could be a good alternative for development of new drugs for the treatment of CL.

En este trabajo se analiza la funcionalidad de una investigación dirigida hacia la búsqueda de sustancias antiparasitarias de la flora colombiana, sus fundamentos y desarrollo. Además se presentan los criterios de selección de los materiales promisorios del proyecto así como de otros ejemplos reportados en la literatura.

Natural products are isolated from biodiversity, that is, from plants, microorganisms, insects, and marine organisms; most of the biodiversity is found in about 10-12 countries located around the Equator. For a long time, people chose this option to alleviate diseases and the industry to discover new medicines; however, from the 70's onwards synthetic products have displaced them. Today there is a rebirth of natural products research and annually hundreds of new natural and synthetic bioactive molecules are reported in specialized journals. On the other hands, new drugs are continually required and especially there is a deficit of them to treat the so-called Neglected Diseases, which affect and threaten the health of billions of people in the world. These diseases paradoxically affect almost all megadiverse countries. Thus, the richest countries in biodiversity do not benefit from the use of natural products because research, development and production of new medicines are carried out in more technologically advanced countries. Why do we have so many molecules in biodiversity and journals but so few medicines? How could new antiparasite drugs be developed quickly and cheaply in the countries affected by Neglected Diseases? A feasible alternative is the Mining in Press, that is, the search of molecules in scientific literature. In this paper we analyze the reasons why these valuable substances have not become drugs and remain curiosities of laboratories and libraries, and the advantages of using this approach as a source of drugs or templates to other bioactive molecules.

Mediante ensayos biodirigídos se aisló de Pycnoporus sanguineus (Polyporaceae) un compuesto activo contra amastigotes de Leishmania (viannia) panamensis; su elucidación estructrual se realizó mediante técnicas espectroscópicas (RMN 1H Y 13C Y Espectrometría de Masas); este producto fue identificado como el ergosterol-5,8-endoperóxido.

Natural products are isolated from biodiversity, that is, from plants, microorganisms, insects, and marine organisms; most of the biodiversity is found in about 10-12 countries located around the Equator. For a long time, people chose this option to alleviate diseases and the industry to discover new medicines; however, from the 70's onwards synthetic products have displaced them. Today there is a rebirth of natural products research and annually hundreds of new natural and synthetic bioactive molecules are reported in specialized journals. On the other hands, new drugs are continually required and especially there is a deficit of them to treat the so-called Neglected Diseases, which affect and threaten the health of billions of people in the world. These diseases paradoxically affect almost all megadiverse countries. Thus, the richest countries in biodiversity do not benefit from the use of natural products because research, development and production of new medicines are carried out in more technologically advanced countries. Why do we have so many molecules in biodiversity and journals but so few medicines? How could new antiparasite drugs be developed quickly and cheaply in the countries affected by Neglected Diseases? A feasible alternative is the Mining in Press, that is, the search of molecules in scientific literature. In this paper we analyze the reasons why these valuable substances have not become drugs and remain curiosities of laboratories and libraries, and the advantages of using this approach as a source of drugs or templates to other bioactive molecules.

En este trabajo se abordó un estudio preliminar sobre la composición de metabolitos secundarios en las hojas de cinco genotipos de tomate de árbol (Cyphomandra betacea) y su papel contra Colletotrchum gloeosporioides, un hongo agente causal de la antracnosis. Se determinaron varias diferencias en el perfil químico de extractos de las hojas de algunos genotipos, así como una alta actividad antibiótica contra este hongo, sugiriendo un papel activo de estas sustancias en la defensa química de la planta.