Edwin Perez - Academia.edu (original) (raw)

Papers by Edwin Perez

ChemInform, 2015

A copper-catalyzed regio-and intermolecular aminofluorination of styrenes has been developed. In ... more A copper-catalyzed regio-and intermolecular aminofluorination of styrenes has been developed. In this reaction Ph-IQ Q QN-Ts and Et 3 NÁ 3HF act as nitrogen and fluorine sources, respectively. The obtained b-fluoro-N-Ts-phenethylamines can be N-alkylated with subsequent deprotection affording the corresponding b-fluoro-N-alkylated phenethylamines, which are interesting building blocks for compounds acting on neuronal targets.

Bioorganic & medicinal chemistry letters, 2009

This study reports the comparative molecular modeling, docking and dynamic simulations of human a... more This study reports the comparative molecular modeling, docking and dynamic simulations of human alpha9alpha10 nicotinic acetylcholine receptors complexed with acetylcholine, nicotine and alpha-conotoxin RgIA, using as templates the crystal structures of Aplysia californica and Lymnaea stagnalis acetylcholine binding proteins. The molecular dynamics simulations showed that Arg112 in the complementary alpha10(-) subunit, is a determinant for recognition in the site that binds small ligands. However, Glu195 in the principal alpha9(+), and Asp114 in the complementary alpha10(-) subunit, might confer the potency and selectivity to alpha-conotoxin RgIA when interacting with Arg7 and Arg9 of this ligand.

The Alkaloids. Chemistry and biology, 2010

Duguetia is one of the larger genera in the family Annonaceae. About 16 out of 100 species have b... more Duguetia is one of the larger genera in the family Annonaceae. About 16 out of 100 species have been examined for alkaloids, and 105 of these compounds have been identified or, if new, their structures have been determined. Many of the isolates are commonly distributed isoquinoline alkaloids. Other alkaloids belong to subgroups specific to this genus or limited to Duguetia

Molecular biology and evolution, 2014

Nicotinic acetylcholine receptors are a family of ligand-gated nonselective cationic channels tha... more Nicotinic acetylcholine receptors are a family of ligand-gated nonselective cationic channels that participate in fundamental physiological processes at both the central and the peripheral nervous system. The extent of calcium entry through ligand-gated ion channels defines their distinct functions. The α9α10 nicotinic cholinergic receptor, expressed in cochlear hair cells, is a peculiar member of the family as it shows differences in the extent of calcium permeability across species. In particular, mammalian α9α10 receptors are among the ligand-gated ion channels which exhibit the highest calcium selectivity. This acquired differential property provides the unique opportunity of studying how protein function was shaped along evolutionary history, by tracking its evolutionary record and experimentally defining the amino acid changes involved. We have applied a molecular evolution approach of ancestral sequence reconstruction, together with molecular dynamics simulations and an evolu...

Chem. Commun., 2015

Proceedings of the 14th Brazilian Meeting on Organic Synthesis Proceedings, 2013

The Alkaloids: Chemistry and Biology, 2010

RSC Advances, 2013

The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, g-glut... more The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, g-glutamylcysteine and glutathione with 3-cinnamoylcoumarin derivatives (ChC1-ChC4) in aqueous solution (30 C, ionic strength 0.2 M KCl) were followed fluorimetrically and evaluated kinetically. The study was completed with a theoretical analysis based on the inverse of the Fukui potential (1/n f (r)), which is proposed for the first time as a local softness descriptor. Thus, considering both experimental results and theoretical analysis, the following conclusions can be drawn: (i) the reactivity of the tested probes towards Michael addition increases in the para-substitution sequence: H < OEt < SMe < Br < NO 2 , and is not correlated with the s P values of the substituents; (ii) in turn, the descriptor proposed here as local softness (1/n f (r)) appears as a promising reactivity index that is able to explain the higher k N values found for both electron-withdrawing and electron-donating groups; (iii) the nucleophilic reactivity of the biothiols employed increases in the sequence Cys-Gly < Hcy < GSH < Cys < g-Glu-Cys; and also finally (iv) we have demonstrated that these probes can be used for fluorimetric thiol determination in SH-SY5Y cells.

Tetrahedron Letters, 2011

Two fluorescence probes for the detection of cysteine (Cys), glutathione (GSH) and other biothiol... more Two fluorescence probes for the detection of cysteine (Cys), glutathione (GSH) and other biothiols, such as homocysteine (Hcy) and cysteinyl-glycine (Cys-Gly), were developed. These molecular probes are coumarin-based derivatives containing a chalcone-like moiety that reacts with biothiols through a Michael addition reaction, leading to strong fluorescence enhancements. The reactivity of the tested biothiols toward both probes (ChC1 and ChC2) follows the order Cys > GSH > Hcy > Cys-Gly, ChC1 being less reactive than ChC2. Possible interference with other amino acids was assessed. ChC1 and ChC2 display a highly selective fluorescence enhancement with thiols, allowing these probes to be used for fluorimetric thiol determination in SH-SY5Y cells.

Natural Product Research, 2003

Dichloromethane extracts of both the roots and the leaves of Raimondia cf. monoica showed in vitr... more Dichloromethane extracts of both the roots and the leaves of Raimondia cf. monoica showed in vitro antiplasmodial and leishmanicidal activities against Plasmodium falciparum and Leishmania panamensis, respectively. Three 6-substituted 5,6-dihydro-2H-pyran-2-ones were isolated. (1) and (2) were identified as (6S)-(5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-oxohepten-1&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;E,3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;E-dienyl)-5,6-dihydro-2H-pyran-2-one (1) and (6R)-(5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-oxohepten-1&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Z,3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;E-dienyl)-5,6-dihydro-2H-pyran-2-one (2), respectively. (-)-Arentilactone (3) was also isolated. The structure of the new compound (1) was determined by spectroscopic methods; additional spectroscopic data for (2) are reported for the first time.

Natural Product Reports, 2012

Covering: up to the end of 2011

MedChemComm, 2013

This work presents the synthesis and the pharmacological characterization of a series of novel 1-... more This work presents the synthesis and the pharmacological characterization of a series of novel 1-(1-benzyl-1H-indol-3-yl)-N,N,N-trimethylmethanaminium iodide derivatives at the human (h) a7 and a4b2 nicotinic acetylcholine receptors (nAChRs). The inhibitory activity of the compounds was determined by Ca 2+ influx assays on cells expressing either the ha7 or ha4b2 nAChR subtype. To determine whether the observed inhibitory activity is mediated by a competitive or non-competitive mechanism, additional radioligand binding assays were performed using [ 3 H]methyllycaconitine, [ 3 H]cytisine, and [ 3 H] imipramine. The results established that the compounds inhibit the nAChRs by a competitive mechanism and that the potencies are higher for the ha7 nAChR compared to that for the ha4b2 nAChR. Substitutions with oxygenated functional groups on the benzene ring increase the receptor selectivity. In particular, the hydroxyl derivatives 4b and 4c present the highest selectivity for the ha7 nAChR subtype. Molecular docking results indicate that the hydroxyl group forms a hydrogen bond with the carbonyl group at a7-Gln116, but not at b2-Phe115, supporting the observed receptor selectivity at the molecular level.

Journal of the Chilean Chemical Society, 2005

ABSTRACT The leaves of Duguetia vallicola, a fairly common, large evergreen tree from the coastal... more ABSTRACT The leaves of Duguetia vallicola, a fairly common, large evergreen tree from the coastal regions of Panama, Colombia and Venezuela, contain (6aS)-glaziovine (1) as a major constituent. The abundance and renewable character of the plant material make it an attractive source for this rare, psychoactive alkaloid. The availability of glaziovine and its 0-methyl derivative pronuciferine (2) has made complete H-1 and C-13 NMR assignments of proaporphines possible for the first time.

Journal of Pharmacy and Pharmacology, 2013

The chemical study of a dichloromethane extract from Azorella compacta was directed to the isolat... more The chemical study of a dichloromethane extract from Azorella compacta was directed to the isolation of characteristic mulinane and azorellane diterpenoids in order to determine their gastroprotective activity. Methods Usual chromatographic techniques on the extract led to the isolation of 12 compounds, which were identified by their spectroscopic properties. The HCl/ ethanol-induced gastric lesions model in mice was used to determine the gastroprotective activity. Key findings The new diterpenoids, 13b-hydroxymulinane (1), mulin-11, 13-dien-20-ol (2), 13a-methoxyazorellanol (3) and mulin-11,13-dien-18acetoxy-16,20-dioic acid (12) were isolated from A. compacta. The known diterpenoids mulin-11,13-dien-20-oic acid (4), 13a-hydroxyazorellane (5), 13bhydroxyazorellane (6), mulinic acid , mulinolic acid (8) and azorellanol (9), and the aromatic compounds 5,7-dihydroxychromone (10) and isoflavonoid biochanin A (11), were also obtained from the extract. Compounds 6, 9 and 12 at 20 mg/kg reduced gastric lesions by 69%, 71% and 73%, respectively, being statistically similar to lansoprazole at the same dose. Conclusions The results corroborate the intraspecific chemical variations detected previously in specimens of A. compacta collected at different Chilean latitudes. A high concentration of azorellanol (9) could account in part for some of the therapeutic properties attributed to this species, in particular in ulcer treatment. Most of the mulinane and azorellane diterpenoids isolated in this study showed relevant gastroprotective activity at a low dose in the bioassay.

Journal of Natural Products, 2007

A new triterpenoid (1) derived from 24-methylcycloartanol was isolated from the leaves of Oxandra... more A new triterpenoid (1) derived from 24-methylcycloartanol was isolated from the leaves of Oxandra cf. xylopioides. An unusual structure of the new compound was assigned as 1, for which the name berenjenol is proposed, on the basis of the spectroscopic data of the natural product and of its derivatives 2 and 3. The leaves also afforded the known monoterpene isoespintanol (4). Compounds 1 and 4 significantly reduced the paw edema induced by carrageenan by 64% and 43%, at 3 h, respectively. Moreover, 4 reduced IL-1 production by 72% at 100 µM and reduced IL-1 mRNA synthesis.

Bioorganic & Medicinal Chemistry Letters, 2013

Some synthetic 1-azabenzanthrones (7H-dibenzo [de,h]quinolin-7-ones) are weakly to moderately cyt... more Some synthetic 1-azabenzanthrones (7H-dibenzo [de,h]quinolin-7-ones) are weakly to moderately cytotoxic, suggesting that they might also show antiparasitic activity. We have now tested a small collection of these compounds in vitro against a chloroquine-resistant Plasmodium falciparum strain, comparing their cytotoxicity against normal human fibroblasts. Our results indicate that 5-methoxy-1-azabenzanthrone and its 2,3-dihydro analogue have low micromolar antiplasmodial activities and showed more than 10-fold selectivity against the parasite, indicating that the dihydro compound, in particular, might serve as a lead compound for further development.

Bioorganic & Medicinal Chemistry Letters, 2009

Molecular dynamics a b s t r a c t This study reports the comparative molecular modeling, docking... more Molecular dynamics a b s t r a c t This study reports the comparative molecular modeling, docking and dynamic simulations of human a9a10 nicotinic acetylcholine receptors complexed with acetylcholine, nicotine and a-conotoxin RgIA, using as templates the crystal structures of Aplysia californica and Lymnaea stagnalis acetylcholine binding proteins. The molecular dynamics simulations showed that Arg112 in the complementary a10(À) subunit, is a determinant for recognition in the site that binds small ligands. However, Glu195 in the principal a9(+), and Asp114 in the complementary a10(À) subunit, might confer the potency and selectivity to a-conotoxin RgIA when interacting with Arg7 and Arg9 of this ligand.