Medicinal Chemistry, Organic Synthesis, Drug Design, Green Chemistry, Zero Effluent Reactions

Textualidades cannábicas

by L. Nicolás Guigou

Ponencia presentada en el Debate Nacional sobre drogas- 29 al 31 de agosto de 2011

APOYA:more Ponencia presentada en el Debate Nacional sobre drogas- 29 al 31 de agosto de 2011

APOYA:
CSIC-UNIVERSIDAD DE LA REPUBLICA, URUGUAY

Título: Textualidades cannábicas.
Prof. Agr. Dr. L. Nicolás Guigou- Núcleo de Antropología de la ContemporaneidadDepartamento de Ciencias Sociales y Humanas, LICCOM, UDELAR.

Introducción.

Parte del proceso de secularización de las culturas, puede ser atendido en tanto
desencantamiento – no del mundo- sino de la naturaleza. La naturaleza desencantada,
exterior, silenciosa –prácticamente la naturaleza del mito de La Caída-, o bien la imagen
clásica que teníamos de la diferenciación entre naturaleza y cultura se ha visto a todas
luces, trastocada. A los filosofemas y mitemas antropológicos que proponían dar a la
naturaleza el lugar de los universales culturales, o meramente de los universales -todo lo
universal es parte de la naturaleza, lo singular, un producto de la cultura-, se le
opusieron procesos teóricos cada vez más secularizantes (como el giro derridadiano)
llegándose en la contemporaneidad a proponerse cambios radicales en nuestra
perspectiva de la naturaleza, la cultura, la percepción y las diferentes formas de
entrelazamiento entre inteligencias humanas y no humanas.
La selva – la naturaleza- se vuelve inteligente, al decir de Descola,
mostrándonos así todas las aristas de una antropología no-humana (post-humana) en la
cual la naturaleza ya no es objeto inteligible, sino sujeto inteligente...

Molecular docking, QPLD, and ADME prediction studies on HIV-1 integrase leads.

by Chandrabose Selvaraj

Med Chem Res DOI 10.1007/s00044-011-9940-6 (Published)

HIV-1 integrase (IN) is an important drug target over the years with diverse therapeutic potential with the objective... more HIV-1 integrase (IN) is an important drug target over the years with diverse therapeutic potential with the objective of designing new chemical entities with enhanced inhibitory potencies against HIV-1 IN. We performed molecular docking, quantum polarized ligand docking (QPLD), ADME screening, and PASS biological activity prediction studies on Raltegravir, Elvitegravir, and newly searched compounds of Cambridge crystallographic database. Best docking and QPLD scores of known and unknown searched compounds were compared using docking score, docking energy, and emodel energy. Moreover, correlation between docking score, docking energy with emodel energy yielded a statistically significant correlation coefficient. The searched compounds were also evaluated with ADME properties and biological activity prediction analysis. These compounds also show good pharmacokinetic properties under the acceptable range including antiviral biological activity prediction. Hence, these compounds could be employed to design ligands with enhanced inhibitory potencies and to predict the potencies of analogs to guide synthesis/or prepare synthetic analogs for second generation drug development against HIV-1 IN.

Design and Synthesis of Thiadiazoles and Thiazoles Targeting the Bcr-Abl T315I Mutant: from Docking False Positives to ATP-Noncompetitive Inhibitors

by Marco Radi

In an effort to optimize our previously identified dual Src/Abl hits, a new series of 1,3,4-thiadiazoles and... more In an effort to optimize our previously identified dual Src/Abl hits, a new series of 1,3,4-thiadiazoles and 1,3-thiazoles were designed and synthesized, paying particular attention to the reduction of their lipophilicity and to the improvement of the affinity towards the drug-resistant T315I mutant. Compound 5 was identified as a promising allosteric inhibitor of the T315I mutant.

Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication

by Marco Radi

Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high... more Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high intrinsic mutation and replication rates of HIV-1 often lead to the emergence of drug resistant strains and consequent therapeutic failure. On this basis, cellular cofactors represent attractive new targets for HIV-1 chemotherapy, since targeting a cellular factor that is required for viral replication should help to overcome the problem of viral resistance. We and others have recently reported the identification of compounds suppressing HIV-1 replication by targeting the cellular DEAD-box helicase DDX3. These results provide a proof-of-principle for the feasibility of blocking HIV-1 infection by rendering the host cell environment less favorable for the virus. The rationale for such an approach and its implications in potentially overcoming the problem of drug resistance related to drugs targeting viral proteins will be discussed in the context of the known cellular functions of the DEAD-box helicase DDX3.