Papers by VERONICA RODRIGUEZ
Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Abstract As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative... more Abstract As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values = 0.015 and 0.005 μM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancer LNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaP cells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays.
On Violence and Tyranny examines historiography as a vehicle for the production of a theory of ty... more On Violence and Tyranny examines historiography as a vehicle for the production of a theory of tyrannicide in the aftermath of the murder of Pedro I de Castilla (1369). The thesis of this work is that by considering the royal chronicle as a vehicle and locus for political theorization, we can appreciate the formulation of a theory of tyrannicide as a medium for dynastic legitimation that is not reducible to political propaganda. Rather, it becomes a meditation about monarchy itself, the limits of power, and the underlying causes and consequences of political violence. The chronicle of the king Pedro's rule conceives an economy of violence coded in terms of saber (political wisdom), justice and the law, as a means to face the ideological, political, and social challenges that civil war and regicide pose to a community. I will focus on two fragments of the chronicle, a pair of letters attributed to a wise Moor that the chronicler chose to include in a second stage of his composition and that establish extra textual connections to other political genres such as the specula principum and political prophecy. Through them, I will explore how a theory of tyrannicide allows the chronicler to confront three major problems that regicide poses. First, how to explicate the dynastic break that king Pedro's murder brought about, and minimize the discontinuity that the advent of a new, and illegitimate, dynasty (the Trastámaras) represented for a historical tradition that deeply valued the continuity of history. Second, how a theory of tyrannicide served to repair the broken ties provoked by the civil war. And third, how to represent that founding violence, the violence against a sovereign, to render it legitimate, but not available for anyone else to exploit.
Gaceta Medica De Mexico, 2014
El melanoma es una de las neoplasias que más ha aumentado en los últimos años; en EE.UU., entre l... more El melanoma es una de las neoplasias que más ha aumentado en los últimos años; en EE.UU., entre los años 1950 y 2000 su incidencia incrementó un 619%. Su tratamiento en etapas avanzadas siempre ha sido un reto y, una vez que se vuelve metastásico, no existe ningún esquema terapéutico curativo. Desde hace algunos años se producen avances significativos en el entendimiento de los cambios genéticos, inmunológicos y moleculares que ocurren en su desarrollo y progresión, y ello ha permitido desarrollar tratamientos moleculares e inmunomoduladores que presentan mejores tasas de respuesta que la quimioterapia (QT) convencional. Aunque el arsenal terapéutico actual es muy amplio, sólo hay ocho medicamentos aprobados por la Food and Drug Administration (FDA). En el siguiente artículo se revisarán los tratamientos sistémicos más relevantes: QT convencional, terapia molecular (inhibidores de la vía proteína cinasa activada por mitógenos [MAPK]) e inmunomoduladora (interleucina 2 [IL-2], interferón α [IFN-α], inhibidores del antígeno 4 de los linfocitos T citotóxicos [CTLA-4] y muerte programada 1 [PD-1]), así como otros misceláneos, entre los que se encuentran los inhibidores de la angiogénesis, los moduladores de la apoptosis celular, las vacunas y la radioterapia.
European Journal of Medicinal Chemistry, 2015
The pure enantiomers of the N-(2-, 3-, and 4-(2-aminocyclopropyl)phenyl)benzamides hydrochlorides... more The pure enantiomers of the N-(2-, 3-, and 4-(2-aminocyclopropyl)phenyl)benzamides hydrochlorides 11aej were prepared and tested against LSD1 and MAO enzymes. The evaluation of the regioisomers 11a ej highlighted a net increase of the anti-LSD1 potency by shifting the benzamide moiety from ortho to meta and mainly to para position of tranylcypromine phenyl ring, independently from their trans or cis stereochemistry. In particular, the para-substituted 11a,b (trans) and 11g,h (cis) compounds displayed LSD1 and MAO-A inhibition at low nanomolar levels, while were less potent against MAO-B. The meta analogs 11c,d (trans) and 11i,j (cis) were in general less potent, but more efficient against MAO-A than against LSD1. In cellular assays, all the para and meta enantiomers were able to inhibit LSD1 by inducing Gfi-1b and ITGAM gene expression, with 11b,c and 11gei giving the highest effects. Moreover, 11b and 11g,h strongly inhibited the clonogenic potential of murine promyelocytic blasts.
MedChemComm, 2015
A new series of pyrrole/indole-containing tranylcypromine analogues is reported as potent and sel... more A new series of pyrrole/indole-containing tranylcypromine analogues is reported as potent and selective LSD1 inhibitors active in leukemia.
ACS Medicinal Chemistry Letters, 2014
The pure four diastereomers (11a−d) of trans-benzyl (1-((4-(2aminocyclopropyl)phenyl)amino)-1-oxo... more The pure four diastereomers (11a−d) of trans-benzyl (1-((4-(2aminocyclopropyl)phenyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate hydrochloride 11, previously described by us as LSD1 inhibitor, were obtained by enantiospecific synthesis/chiral HPLC separation method. Tested in LSD1 and MAO assays, 11b (S,1S,2R) and 11d (R,1S,2R) were the most potent isomers against LSD1 and were less active against MAO-A and practically inactive against MAO-B. In cells, all the four diastereomers induced Gfi-1b and ITGAM gene expression in NB4 cells, accordingly with their LSD1 inhibition, and 11b and 11d inhibited the colony forming potential in murine promyelocytic blasts.
European Journal of Medicinal Chemistry, 2014
Recently we described some (thiazol-2-yl)hydrazones as antiprotozoal, antifungal and anti-MAO age... more Recently we described some (thiazol-2-yl)hydrazones as antiprotozoal, antifungal and anti-MAO agents as well as Gcn5 HAT inhibitors. Among these last compounds, CPTH2 and CPTH6 showed HAT inhibition in cells and broad anticancer properties. With the aim to identify HAT inhibitors more potent than the two prototypes, we synthesized several new (thiazol-2-yl)hydrazones including some related thiazolidines and pyrimidin-4(3H)-ones, and we tested the whole library existing in our lab against human p300 and PCAF HAT enzymes. Some compounds (1x, 1c', 1d', 1i' and 2m) were more efficient than CPTH2 and CPTH6 in inhibiting the p300 HAT enzyme. When tested in human leukemia U937 and colon carcinoma HCT116 cells (100 μM, 30 h), 1x, 1i' and 2m gave higher (U937 cells) or similar (HCT116 cells) apoptosis than CPTH6, and were more potent than CPTH6 in inducing cytodifferentiation (U937 cells).
EN LA PRESENTE TESIS DOCTORAL SE HA INTENTADO DE MODO PARTICULAR ABORDAR EL PROBLEMA DE LA ESTABI... more EN LA PRESENTE TESIS DOCTORAL SE HA INTENTADO DE MODO PARTICULAR ABORDAR EL PROBLEMA DE LA ESTABILIZACION DE ENZIMAS QUE INTERVIENEN EN PROCESOS DE ENORME INTERES COMO ES LA OBTENCION DE 7-ACA A PARTIR DE CEFALOSPORINA C, PARA LA SINTESIS DE ANTIBIOTICOS BETA-LACTAMICOS. ESTAS ENZIMAS PRESENTAN BUENAS CARACTERISTICAS INTRINSECAS COMO CATALIZADORES PERO SU COMPLEJIDAD DE ESTRUCTURA (SON ENZIMAS DIMERICAS CON COFACTORES) Y SU SUSCEPTIBILIDAD A SER INACTIVADAS POR EL PEROXIDO DE HIDROGENO PRESENTE EN LA REACCION QUE CATALIZAN, AUMENTAN RESPECTO A OTRAS ENZIMAS LA DIFICULTAD DE SU ESTABILIZACION. AL ENFRENTARNOS A LA ESTABILIZACION DE DOS D-AMINOACIDO OXIDASAS PROCEDENTES DE DISTINTA FUENTE Y UNA GLUTARIL ACILASA, HEMOS DESARROLLADO DISTINTAS ESTRATEGIAS DE INMOVILIZACION Y ENTRECRUZAMIENTO PARA ESTABILIZAR SU ESTRUCTURA CUATERNARIA, EN ESTE SENTIDO LOS RESULTADOS OBTENIDOS NOS HAN PROPORCIONADO MUY BUENOS PARAMETROS DE ESTABILIDAD EN LAS TRES ENZIMAS ESTUDIADAS. HEMOS ESTUDIADO LOS DIS...
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Papers by VERONICA RODRIGUEZ