Actualmente en Lima Metropolitana, 7 de cada 10 personas consumen bebidas alcohólicas como la cerveza y el trago corto. Este hecho origina que casi el 90% de estas personas padezcan resaca por alcohol, producto de la ingesta excesiva y/o la mezcla de estas bebidas, originando malestar general acompañado de dolor de cabeza, náuseas, mareos y dolor estomacal. Los momentos más frecuentes de consumo que se presentan son los fines de semana, festividades, feriados y fines de mes. Los consumos de las bebidas alcohólicas se presentan en su mayoría en reuniones, fiestas, integraciones familiares, amicales y de trabajo. Para solucionar esta problemática identificada hemos creado R-BORN, una Bebida hecha a base de insumos naturales, teniendo como propuesta de valor principal aliviar el malestar y mitigar los síntomas de la resaca con productos naturales. Esta bebida está hecha a base de tres frutas, las cuales son la tuna, piña y coco, debido a sus componentes y propiedades que permiten contrarrestar los efectos del alcohol. Nuestro producto va dirigido para hombres y mujeres mayores de 18 años hasta los 39 años de edad, que pertenezcan a un nivel socioeconómico A y B, que padezcan el malestar de resaca producto de la ingesta excesiva de bebidas alcohólicas y prefieran combatirla con un producto hecho a base de insumos naturales. Nuestro tamaño de mercado estimado es de 390,378 personas. Asimismo, este producto será comercializado a través de los siguientes canales de ventas: bodegas, ferias saludables, sitio web, redes sociales y venta directa. / Currently in Lima Metropolitan 7 out of 10 people, consume alcoholic beverages such as beer and short drink. This fact results in almost 90% of these people developing alcohol hangover caused by an excessive intake and/or the mixture of these drinks, producing general discomfort accompanied by headache, nausea, dizziness and stomach pain. The most frequent times of consumption that occur are weekends, holidays and weekends. Consumption of alcoholic beverages are the mostly presented in meetings, parties, and family, amical and work integrations. To solve this identified problem we have created R-BORN, a drink made from natural inputs having as its main value proposition to alleviate the discomfort and mitigate hangover symptoms with natural products. This drink is made from three fruits, which are tuna, pineapple and coconut because of its components, and properties that counteract the effects of alcohol. Our product is aimed at men and women over the age of 18 up to the age of 39 who belong to a socioeconomic level A and B who suffer from hangover discomfort resulting from excessive alcoholic beverages and preferring to fight it with a product made from natural supplies. Our estimated market size is 390,378 people. In addition, this product will be marketed through the following sale’s channels: grocery stores, healthy food fairs, website, social networks and direct selling. / Trabajo de investigación

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The first semi-synthesis of (-)-melodinine K was completed from the monoterpene indole alkaloid (-)-tabersonine through regioselective enzymatic hydroxylation and Polonovski-Potier coupling. Regioselective borylation strategies were used to achieve meta-oxygenated derivatives of (-)-tabersonine for analysis in a Drosophila fruit fly Alzheimer’s phenotype model. A library of oxygenated and epoxidized bis-indole alkaloid analogs in the taberyunine class were prepared to conduct a structure activity relationship (SAR) study of the bis-indole framework against colon cancer and melanoma cell lines. Alkaloid aryl trifluoroborates were synthesized to increase nucleophilicity of arenes for unfavored alpha-arylations of tertiary amines on route to melosuavine bis-indole alkaloids. Overall, nine new bis-indole alkaloids were synthesized in the melodinine, taberyunine, and melosuavine class that showed strong cytotoxicity against a variety of melanoma, colon cancer, and renal cancer cell lines. / Chemistry

As the spread of antibiotic resistance threatens our ability to treat infections, avoiding the return of a pre-antibiotic era urgently requires the discovery of novel antibiotics. Actinomycetes, a family of bacteria commonly isolated from soil, are a proven source of clinically useful antibiotics. However, easily identifiable metabolites have been exhausted and the rediscovery of common antibiotics thwarts searches for rarer molecules. Sequencing of actinomycete genomes reveals that they contain far more biosynthetic gene clusters with the potential to encode antibiotics than whose products can be readily observed in the laboratory. The work presented in this thesis revolves around developing approaches to mine these previously inaccessible metabolites as a source of new antibiotics. First, I describe how inactivation of biosynthetic gene clusters for common antibiotics can uncover rare antibiotics otherwise masked in these strains. By applying CRISPR-Cas9 to knockout genes encoding nuisance antibiotics, I develop a simple strategy to reveal the hidden biosynthetic potential of actinomycete strains that can be used to discover rare or novel antibiotics. Second, I describe the use of the evolutionary history of biosynthetic gene clusters to prioritize divergent members of an antibiotic family, the glycopeptide antibiotics, that are likely to possess new biological activities. Using these predictions, I uncover a novel functional class of glycopeptide antibiotics that blocks the action of autolysins, essential peptidoglycan hydrolases required for remodelling the cell wall during growth. Finally, I apply target-directed genome mining, which makes use of target duplication as a predicted resistance mechanism within an antibiotic’s biosynthetic gene cluster. Using this approach, I discover the association of a family of gene clusters with the housekeeping protease ClpP and characterize the produced metabolite’s effect on ClpP function. These three research projects mine previously inaccessible chemical matter from a proven source of antibiotics, actinomycetes. The techniques and antibiotics described are required now more than ever to develop life-saving antibiotics capable of combatting multidrug-resistant pathogens. / Dissertation / Doctor of Philosophy (PhD) / Antibiotics are essential for treating life-threatening infections, but the rise of antibiotic resistance renders them ineffective. To treat these drug-resistant infections, new antibiotics that work in new ways are required. A family of bacteria commonly isolated from soil called Actinomycetes produce most antibiotics we use today, but it has become increasingly difficult to find new antibiotics from this source. My work describes three techniques that can be applied to actinomycetes to help overcome the challenges associated with antibiotic discovery. Specifically, these techniques guide discovery efforts by making use of regions in actinomycete genomes called biosynthetic gene clusters that often encode antibiotics. In doing so, I describe ways to uncover rare antibiotics from actinomycete strains that produce common and uninteresting antibiotics, use antibiotic family trees to discover antibiotics that work in new ways, and apply antibiotic resistance to identify biosynthetic gene clusters likely to act on a certain bacterial target.

Underexplored environments such as soil samples continue to be an untapped source of bacterial strains with great potential to produce secondary metabolites for medicinal applications. As a result, these microorganisms represent a broad and yet unknown reservoir of new strains capable of producing these novel compounds. The current research primarily seeks to perform the isolation, purification, and characterization of secondary metabolites from a soil bacterium (Janthinobacterium lividum TAJX1901). The isolated soil bacterium was successfully cultured on rich media agar plates, followed by extraction using methanol and chloroform. The purification methods utilized include flash column chromatography, preparative thin-layer chromatography, and high-performance liquid chromatography. For structural elucidation, UV-Vis analysis, infrared spectroscopy, and nuclear magnetic resonance spectroscopy were employed. The extraction resulted in a dominant violet pigment soluble in methanol. Results revealed the presence of highly conjugated, polar, and aromatic compounds (violacein or relatives of violacein) and dioctyl phthalate (a contaminant).

<p>Natural products, along with natural product derivatives, are known to be at the root of the development of many pharmaceuticals, oftentimes showing unique bioactivity against interesting targets. Specifically, natural products containing furans show activity against a variety of diseases including fungal infections, and cancers. It is hypothesized that unknown natural products containing furans could show more potent or other biological activities. However, it is challenging to discover and isolate these small molecules from cell supernatant. The work described herein showcases the development of a molecular probe that can covalently attach to furan moieties via a [4 + 2] Diels-Alder cycloaddition, making them easily identifiable on liquid chromatography mass spectroscopy (LC-MS). The molecular probe, which undergoes this reaction with a variety of furans, was designed with both a UV-tag and a mass tag to enable easy identification. The probe has been tested with a variety of purified furans, including natural products, methylenomycin furan (MMF) hormones, and MMF derivatives. Moreover, work has begun to test the molecular probe in cell supernatants. </p>

Drimane and coloratane sesquiterpenoids are present in several plants, microorganisms, and marine life. Because of their cytotoxic activity, these sesquiterpenoids have received increasing attention as a source for new anticancer drugs and pharmacophores. Natural drimanes and coloratanes, as well as their semi-synthetic derivatives, showed promising results against cancer cell lines with in vitro activities in the low micro- and nanomolar range. Despite their high potential as novel anticancer agents, the mode of action and structure–activity relationships of drimanes and coloratanes have not been completely enlightened nor systematically reviewed. Our review aims to give an overview of known structures and derivatizations of this class of sesquiterpenoids, as well as their activity against cancer cells and potential modes-of-action. The cytotoxic activities of about 40 natural and 25 semi-synthetic drimanes and coloratanes are discussed. In addition to that, we give a summary about the clinical significance of drimane and coloratane sesquiterpenoids.

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No description available.

Underexplored environments such as soil samples continue to be an untapped source of bacterial strains with great potential to produce potent secondary metabolites for medicinal applications. As a result, these microorganisms represent a broad and yet unknown reservoir of new strains capable of producing these novel natural compounds. Secondary metabolites from microorganisms have been used in antibiotic production, chemotherapy, immunosuppressants, and various industrial applications. The current research primarily seeks to perform the isolation, purification, and characterization of secondary metabolites from a soil bacterium (Janthinobacterium lividum TAJX1901). To achieve these objectives, the soil bacteria was successfully cultured on rich media agar plates followed by liquid–liquid extraction using a solvent mixture of methanol and chloroform(3:1). Various purification methods were utilized, including flash column chromatography, preparative thin layer chromatography, centrifugation, and high-performance liquid chromatography (HPLC ) using different column types and elution methods. For structural elucidation, UV/Vis analysis, infrared spectroscopy, and nuclear magnetic resonance spectroscopy were employed. The extraction resulted in a dominant violet pigment soluble in methanol. Preliminary results reveal the presence of highly conjugated, polar, and aromatic compounds. This work is relevant in the current global search for novel compounds for tackling antibiotic-resistant organisms and treating other diseases and infections.