Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines

265 páginas : ilustraciones, gráficas

Autores:: Romero Salamanca, Juan Manuel
Castañeda Castellanos, Brian Alonso

Tipo de recurso:: Trabajo de grado de pregrado

Fecha de publicación:: 2019

Institución:: Universidad de Ciencias Aplicadas y Ambientales U.D.C.A

Repositorio:: Repositorio Institucional UDCA

Idioma:: spa

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dc.title.spa.fl_str_mv	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
title	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
spellingShingle	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines Ciclooxigenasa 1 Ciclooxigenasa 2 Cannabis sativa Cannabis Inflamación Dolor Ciclooxigenasa 1 Ciclooxigenasa 2 Energía de libre unión
title_short	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
title_full	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
title_fullStr	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
title_full_unstemmed	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
title_sort	Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines
dc.creator.fl_str_mv	Romero Salamanca, Juan Manuel Castañeda Castellanos, Brian Alonso
dc.contributor.advisor.spa.fl_str_mv	Malagón Bernal, Rafael Eduardo, dir.
dc.contributor.author.spa.fl_str_mv	Romero Salamanca, Juan Manuel Castañeda Castellanos, Brian Alonso
dc.subject.mesh.spa.fl_str_mv	Ciclooxigenasa 1 Ciclooxigenasa 2
topic	Ciclooxigenasa 1 Ciclooxigenasa 2 Cannabis sativa Cannabis Inflamación Dolor Ciclooxigenasa 1 Ciclooxigenasa 2 Energía de libre unión
dc.subject.lemb.spa.fl_str_mv	Cannabis sativa
dc.subject.proposal.spa.fl_str_mv	Cannabis Inflamación Dolor Ciclooxigenasa 1 Ciclooxigenasa 2 Energía de libre unión
description	265 páginas : ilustraciones, gráficas
publishDate	2019
dc.date.accessioned.spa.fl_str_mv	2019-04-29T16:40:04Z
dc.date.available.spa.fl_str_mv	2019-04-29T16:40:04Z
dc.date.issued.spa.fl_str_mv	2019
dc.type.spa.fl_str_mv	Trabajo de grado - Pregrado
dc.type.coarversion.fl_str_mv	http://purl.org/coar/version/c_970fb48d4fbd8a85
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dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/bachelorThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/publishedVersion
dc.type.content.spa.fl_str_mv	Text
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dc.identifier.uri.spa.fl_str_mv	https://repository.udca.edu.co/handle/11158/1376
dc.identifier.local.spa.fl_str_mv	QF018 R65m 2019 (205481)
url	https://repository.udca.edu.co/handle/11158/1376
identifier_str_mv	QF018 R65m 2019 (205481)
dc.language.iso.spa.fl_str_mv	spa
language	spa
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spelling	Malagón Bernal, Rafael Eduardo, dir.Romero Salamanca, Juan ManuelCastañeda Castellanos, Brian Alonso2019-04-29T16:40:04Z2019-04-29T16:40:04Z2019https://repository.udca.edu.co/handle/11158/1376QF018 R65m 2019 (205481)265 páginas : ilustraciones, gráficasEn el represente estudio se determinó la interacción molecular de los metabolitos conocidos en la especie Cannabis sativa L. con las dos isoformas de la enzima ciclooxigenasa (COX1 y COX2) de Homo sapiens, a partir del uso de técnicas computacionales de modelamiento por homología y acoplamiento (docking). Se modelaron por medio de homología de proteínas las dos isoformas enzimáticas COX1 y COX2 de Homo sapiens, obteniéndose modelos teóricos moleculares validos según el grafico de Ramachandran. Además, se sometieron los modelos obtenidos a un acoplamiento molecular con dos compuestos endógenos: ácido araquidónico y PGG2, y dos fármacos de actividad conocida: Flurbiprofeno y Celecoxib. Dichos acoplamientos fueron establecidos en los sitios catalíticos peroxidasa, para la enzima COX1 y ciclooxigenasa, para la enzima COX2, demostrando la idoneidad de los modelos para el posterior cribado virtual. Por otro lado, los 113 compuestos seleccionados, provenientes de la especie Cannabis sativa L. fueron evaluados a partir de los criterios establecidos por Lipinski, en donde 93 de los compuestos cumplieron con todos los criterios. El metabolito de biotransformación mayoritario de cada uno de los 93 compuestos fue determinado, por medio de revisión bibliográfica, siendo la adición de grupos hidroxilos la reacción más frecuente en todos los compuestos. Los 93 compuestos seleccionados y sus metabolitos de biotransformación fueron sometidos a un proceso de cribado virtual, en donde se establecieron cuatro categorías de estudio y se seleccionaron los primeros cuatro compuestos o metabolitos de biotransformación con el valor de energía libre de unión (ΔG) y constante de inhibición (ki) más bajo en cada una de las categorías. El primer cribado virtual fue realizado para los 93 compuestos producto de biosíntesis en la especie Cannabis sativa L y la enzima COX1 (CATEGORIA I), el segundo relacionó los mismos compuestos y la enzima COX2 (CATEGORIA II); en la tercera categoría se efectuó el cribado virtual entre los productos de biotransformación y la COX1 (CATEGORIA III), y la cuarta categoría dichos productos de biotransformación fueron evaluados frente a la COX2 (CATEGORIA IV). Para la primera categoría se seleccionaron los siguientes compuestos: Friedelin, Delta-7-cis-isotetrahidrocannabivarina, Cannabinol-C2 y Epifriedelanol. En la Categoría II fueron seleccionados los siguientes compuestos: Delta-9-tetrahidrocannabinol, Cannabiorcol, Delta-9-tetrahidrocannabivarina y 10-oxo-delta-6a-tetrahidrocannabinol. En la Categoría III los metabolitos de biotransformación que siguen fueron seleccionados: Luteolin, Friedelin, Ácido delta-9-tetrahidrocannabinolico A y 3,3’-dihydroxy-5,4’-dimethoxy bibenzyl. Finalmente, en la Categoría IV fueron seleccionados los siguientes metabolitos de biotransformación: Luteolin, Delta-9-tetrahidrocannabivarina, Delta-7- cis-iso-tetrahidrocannabivarina y Cannabinol-C2. Los cuatro compuestos y los cuatro metabolitos de biotransformación seleccionados en el cribado virtual con el modelo teórico molecular de la enzima COX1 y COX2, respectivamente fueron sometidos a un proceso de acoplamiento molecular con las enzimas correspondientes. Todos los compuestos y metabolitos de biotransformación acoplados con la enzima COX1, presentaron interacciones de tipo hidrofóbico, pi-pi y catión-pi con aminoácidos importantes en el sitio catalítico peroxidasa (GLN203, HIS207 y PHE409). En contraste, siete de los compuestos acoplados con la enzima COX2 se unieron al sitio activo ciclooxigenasa y presentaron interacciones con aminoácidos involucrados en la reacción catalítica ciclooxigenasa (TYR248, VAL349, TYR355, TYR385 y SER530) excepto el metabolito de biotransformación Luteolin-7- glucósido, quien se unió al sitio activo catalítico peroxidasa, debido a su bajo valor de coeficiente de partición octanol:agua. Además, este metabolito fue el único compuesto evaluado que mostró una interacción tipo puente de hidrógeno. El tamaño de los compuestos y su hidrofobicidad puede estar implicado en la selectividad frente a los dos sitios activos catalíticos de las isoformas estudiadas. Así, los compuestos posible candidatos a fármacos inhibidores de la enzima COX1 se ven representados en los compuestos pertenecientes a la clase terpénica (Friedelin, Epifriedelanol y el metabolito de biotransformación del Friedelin), debido a su potencia. La alta selectividad del terpeno Friedelin frente al modelo teórico de la enzima COX1 de Homo sapiens, permite que dicho compuesto sea una alternativa viable al desarrollo de un posible fármaco. La subclase cannabinoide delta-9-tetrahidrocannabinol, por otro lado, presenta una inhibición selectiva frente al modelo teórico de la enzima COX2 de Homo sapiens, con una alta afinidad de unión. Los compuestos cannabinoides han sido ampliamente estudiados frente a su acción terapéutica, sin embargo, nuestros resultados demuestran que en otras clases fitoquímicas de compuestos pueden encontrarse una alternativa al tratamiento del dolor y la inflamaciónIn the present study, the molecular interaction of the metabolites known in the Cannabis sativa L. species with the two isoforms of the enzyme cyclooxygenase (COX1 and COX2) of Homo sapiens was determined, from the use of computational techniques of modeling by homology and coupling (docking). The two COX1 and COX2 enzymatic isoforms of Homo sapiens were modeled by means of protein homology, obtaining valid molecular theoretical models according to the Ramachandran graph. In addition, the obtained models were subjected to a molecular coupling with two endogenous compounds: arachidonic acid and PGG2, and two drugs of known activity: Flurbiprofen and Celecoxib. These couplings were established in peroxidase catalytic sites, for the enzyme COX1 and cyclooxygenase, for the COX2 enzyme, demonstrating the suitability of the models for subsequent virtual screening. On the other hand, the 113 selected compounds, from the Cannabis sativa L. species were evaluated based on the criteria established by Lipinski, where 93 of the compounds met all the criteria. The major biotransformation metabolite of each of the 93 compounds was determined by means of a literature review, the addition of hydroxyl groups being the most frequent reaction in all the compounds. The 93 selected compounds and their biotransformation metabolites were subjected to a virtual screening process, where four study categories were established and the first four biotransformation compounds or metabolites were selected with the value of binding-free energy (ΔG) and constant of inhibition (ki) lower in each of the categories. The first virtual screening was performed for the 93 compounds produced by biosynthesis in the species Cannabis sativa L and the enzyme COX1 (CATEGORY I), the second related the same compounds and the enzyme COX2 (CATEGORY II); in the third category, virtual screening was carried out between the biotransformation products and the COX1 (CATEGORY III), and the fourth category said biotransformation products were evaluated against the COX2 (CATEGORY IV). For the first category, the following compounds were selected: Friedelin, Delta-7-cis-isotetrahydrocannabivarin, Cannabinol-C2 and Epifriedelanol. In Category II the following compounds were selected: Delta-9- tetrahydrocannabinol, Cannabiorcol, Delta-9-tetrahydrocannabivarin and 10-oxo-delta-6a-tetrahydrocannabinol. In Category III the following biotransformation metabolites were selected: Luteolin, Friedelin, Delta-9-tetrahydrocannabinol A and 3,3'-dihydroxy-5,4'-dimethoxy bibenzyl. Finally, in Category IV the following biotransformation metabolites were selected: Luteolin, Delta-9-tetrahydrocannabivarin, Delta-7- cis-iso-tetrahydrocannabivarin and Cannabinol-C2. The four compounds and the four metabolites of biotransformation selected in the virtual screening with the theoretical molecular model of the enzyme COX1 and COX2, respectively, were subjected to a process of molecular coupling with the corresponding enzymes. All the biotransformation compounds and metabolites coupled with the COX1 enzyme showed interactions of hydrophobic type, pi-pi and cation-pi with important amino acids in the catalytic peroxidase site (GLN203, HIS207 and PHE409). In contrast, seven of the compounds coupled with the COX2 enzyme were linked to the active site cyclooxygenase and presented interactions with amino acids involved in the cyclooxygenase catalytic reaction (TYR248, VAL349, TYR355, TYR385 and SER530) except the biotransformation metabolite Luteolin-7- glucoside, who joined the peroxidase catalytic active site, due to its low partition coefficient octanol: water. In addition, this metabolite was the only compound evaluated that showed a hydrogen-bond type interaction. The size of the compounds and their hydrophobicity may be involved in the selectivity towards the two catalytic active sites of the isoforms studied. Thus, the possible candidate compounds for drugs that inhibit the COX1 enzyme are represented in the compounds belonging to the terpenic class (Friedelin, Epifriedelanol and the biotransformation metabolite of Friedelin), due to their potency. The high selectivity of the Friedelin terpene compared to the theoretical model of the COX1 enzyme of Homo sapiens, allows this compound to be a viable alternative to the development of a possible drug. The cannabinoid subclass delta-9-tetrahydrocannabinol, on the other hand, exhibits a selective inhibition against the theoretical model of the COX2 enzyme of Homo sapiens, with a high binding affinity. 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en las Obras Colectivas;
b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda;
c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas.Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).
4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:
a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).
b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.
c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.
d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.
ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.
e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, Acinpro), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.
5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
7. Término.
a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.
b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.
8. Varios.
a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.
b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.
c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.
d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.



Modelo de interacción molecular de metabolitos presentes en la especie Cannabis satival con la enzima ciclooxigebasa-1 (COX1) y la enzima ciclooxigensa-2 (COX2) de homo sapines

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