Wanda P. Almeida

Reação de Baylis-Hillman: uma estratégia para a preparação de intermediários multifuncionalizados para síntese orgânica

The Baylis-Hillman reaction has significantly advanced in the last ten years as demonstrated by a number of applications described in the literature. In this report we show some aspects of this reaction, including scope, limitations and perspectives.

An easy and stereoselective synthesis of N-boc-dolaproine via the Baylis-Hillman reaction

Abstract In this communication we report a stereoselective total synthesis of N -Boc-dolaproine (Dap), an amino acid residue of the antineoplastic pentapeptide Dolastatin 10. Our strategy is based on a Baylis–Hillman reaction between N -Boc-prolinal and methyl acrylate, followed by a diastereoselective double bond hydrogenation and hydrolysis of the ester function.

Glutationa e enzimas relacionadas: papel biológico e importância em processos patológicos

Glutathione (GSH) and related enzymes are pivotal for the normal functioning of several important biological processes. In this review we discuss the biosynthesis and the catalytic cycles of glutathione as well as the major GSH-related enzymes. We also present how glutathione and enzymes are involved in cancer and the chromatographic and non-chromatographic methods used to analyze glutathione and/or its derivatives.

An efficient synthesis of (R)-(−)-baclofen

Abstract In this report we describe an efficient synthesis of ( R )-(−)-baclofen, a selective GABA B agonist used as an antispastic agent. Our strategy is based on an enantioselective deprotonation of a cyclobutanone easily obtained by [2+2] cycloaddition of 4-chlorostyrene and dichloroketene.

A Simple and Stereoselective Synthesis of (+)-β-Piperonyl-γ-Butyrolactone

Abstract A stereoselective synthesis of the title compound based on a diastereoselective alkylation of a chiral enolate derived from Evans oxazolidinone is described.

Glicoproteína-P, resistência a múltiplas drogas (MDR) e relação estrutura-atividade de moduladores

Multidrug resistance, MDR is a major obstacle for cancer chemotherapy. MDR can be reversed by drugs that vary in their chemical structure and main biological activity. Many efforts have been done to overcome MDR based on studies of structure-activity relationships and in this review we summarize some aspects of MDR mediated by P-glycoprotein (P-gp), as the most experimentally and clinically tested form of drug resistance. The most significant MDR mechanisms revealed until now are shortly discussed. Physicochemical and structural properties of MDR modulators, measures of the MDR reversal, and QSAR studies are included.

A stereoselective synthesis of Malbranicin

Abstract In this communication we describe the first synthesis of Malbranicin, a novel antibiotic quinone, isolated from Malbranchea cinnamomea . Our strategy was based on a diastereoselective alkylation of a chiral oxazolidinone enolate. Our results suggest the absolute configuration of this compound.

β-lactam antibiotics epitope mapping with STD NMR spectroscopy: a study of drug-human serum albumin interaction

Molecular recognition events are key issues in many biological processes. STD NMR (saturation transfer difference nuclear magnetic resonance spectroscopy) is one of the techniques used to understand such biological interactions. Herein, we have investigated the interactions of four β-lactam antibiotics belonging to two classes (cephalosporins and penicillins) with human serum albumin (HSA) by 1H STD NMR revealing that the interaction between the aromatic moiety and HSA is responsible for the binding efficiency. Thus, the structural differences from the five to six-membered thio ring in penicillins and cephalosporins do not seem to influence antibiotic-albumin interactions.

Synthesis of Novel 2-Aryl-3-(2-morpholinoethyl)-1,3-thiazinan-4-ones Via Ultrasound Irradiation

This study describes the synthesis of fourteen thiazinanones from a multicomponent reaction of 2-morpholinoehtylamine (as primary amine), arenealdehydes (as carbonyl compound) and the mercaptopropionic acid using both conventional (thermal heating) and ultrasound methodologies. Through thermal heating methodology, the thiazinanones were obtained in 49 to 97% yields for 16 hours and through sonochemistry methodology, the reaction time was reduced for 25 minutes with yields 41 to 88%. The full identification and characterization of unpublished heterocycles were achieved by proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and infrared. Some of them were also characterized by elemental analysis.

Effect on Acetylcholinesterase and Anti-oxidant Activity of Synthetic Chalcones having a Good Predicted Pharmacokinetic Profile

BACKGROUND Acetylcholinesterase (AChE) is an important target in the development of drug to treat Alzheimers disease (AD). In this work, we investigated the effect of twenty-two synthesized chalcones on AChE activity. OBJECTIVE This work is aimed to synthesize and evaluate the effect of chalcones on the AChE activity, as well as anti-oxidant activity and predict their pharmacokinetic profile. METHOD Chalcones were synthesized through a Claisen-Schmidt condensation and their inhibitory effect on the AChE was evaluated by the Elmanns colorimetric method. To determine the anti-oxidant activity the DPPH radical scavenging method was chosen. RESULTS We found that all chalcones inhibit this activity, with IC50 values ranging from 0.008 to 4.8 µM. We selected the most active compound 19 with an IC50 value of 0.008 µM for a kinetic study demonstrating a competitive inhibition mode. Molecular docking simulations showed a good interaction between 19 and the active site of AChE. Considering the prediction of pharmacokinetic parameters being a useful tool for selecting potential drug candidates, our study results suggest that the majority of chalcones, including the most active one, have a promising pharmacokinetic profile and blood-brain barrier permeability. The involvement of reactive oxygen species (ROS) in AD-related events has encouraged us to evaluate these chalcones as radical scavengers. CONCLUSION We have found that compound 19 is a potent AChE inhibitor, and based on kinetic studies, it acts as a competitive inhibitor.