Joaquim F. M. da Silva

The chemistry of isatins: a review from 1975 to 1999

Isatins (1H-indole-2,3-dione) are synthetically versatile substrates, where they can be used for the synthesis of a large variety of heterocyclic compounds, such as indoles and quinolines, and as raw material for drug synthesis. Isatins have also been found in mammalian tissue and their function as a modulator of biochemical processes has been the subject of several discussions. The advances in the use of isatins for organic synthesis during the last twenty-five years, as well as a survey of its biological and pharmacological properties are reported in this review and in the accompanying supplementary information.

Molecular features of the prazosin molecule required for activation of Transport-P.

Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.

A Green Preparation of N -Chloro- and N -Bromosaccharin

Abstract The reaction of the sodium salt of saccharin, potassium chloride or bromide and oxone® in water at room temperature for 24 h produced pure N-chloro- and N-bromosaccharin in 58% and 64% yield, respectively.

N-Chloro and N-bromosaccharins: valuable reagents for halogenation of electron rich aromatics and cohalogenation of alkenes

N-Chloro- and N-bromosaccharins react with electron rich aromatic compounds (anisole, acetanilide, N,N-dimethylaniline) producing halogenated compounds. The reaction with N-bromosaccharin gives para- substituted compounds only, whereas N-chlorosaccharin produces orto and para mixtures (para isomer predominantly, ca. 4-5 : 1). The reactions of the N-halosaccharins with alkenes (cyclohexene, styrene, a-methylstyrene, and 1-hexene) give the corresponding halohydrins.

Brazilian propolis protects Saccharomyces cerevisiae cells against oxidative stress

Propolis is a natural product widely used for humans. Due to its complex composition, a number of applications (antimicrobial, antiinflammatory, anesthetic, cytostatic and antioxidant) have been attributed to this substance. Using Saccharomyces cerevisiae as a eukaryotic model we investigated the mechanisms underlying the antioxidant effect of propolis from Guarapari against oxidative stress. Submitting a wild type (BY4741) and antioxidant deficient strains (ctt1Δ, sod1Δ, gsh1Δ, gtt1Δ and gtt2Δ) either to 15 mM menadione or to 2 mM hydrogen peroxide during 60 min, we observed that all strains, except the mutant sod1Δ, acquired tolerance when previously treated with 25 μg/mL of alcoholic propolis extract. Such a treatment reduced the levels of ROS generation and of lipid peroxidation, after oxidative stress. The increase in Cu/Zn-Sod activity by propolis suggests that the protection might be acting synergistically with Cu/Zn-Sod.

An efficient and new protocol for phosphine-free Suzuki coupling reaction using palladium-encapsulated and air-stable MIDA boronates in an aqueous medium

A simple methodology that uses a system based on polyurea microencapsulated palladium (PdEnCat 30™) and aryl or (2-pyridyl) MIDA boronates for Suzuki–Miyaura cross-coupling reactions of (hetero)aryl halides in water–alcohol under phosphine-free conditions was developed.

Dynamical behaviour of the human β1-adrenoceptor under agonist binding

The human β1-adrenoceptor (hβ1AR) is a transmembrane (TM) protein responsible for the signal transduction pathway via agonist interaction. Despite its importance, hβ1AR activation mechanism is still unclear. The most studied and widely accepted mechanism is the disruption of a salt bridge between TM3 arginine and TM6 glutamic acid, called ionic lock. In this work, we constructed a functional hβ1AR-model equilibrated in a membrane environment to study the influence of agonist binding on the dynamical behaviour of hβ1AR and on the opening of the ionic lock. The results indicate that the agonist (R-noradrenaline) disturbs the hβ1AR, causing a TM helices rotation, disrupting the ionic lock. This rotational motion occurs in opposite directions in the intercellular and extracellular domains of hβ1AR, opening the ionic lock.

Solvent free, microwave assisted conversion of aldehydes into nitriles and oximes in the presence of NH2OH x HCl and TiO2.

Aromatic aldehydes bearing electron-donating groups are easily converted into their respective nitriles using NH2OH·HCl and TiO2 under microwave irradiation, while those bearing an electron-withdrawing group give the corresponding oximes.

N-halossacarinas: reagentes úteis (e alternativos) em síntese orgânica

N-halosaccharins proved to be useful and alternative reagents for diverse organic transformations, such as halogenation of aromatic compounds, benzylic and a-carbonylic positions, cohalogenation of alkenes, oxidation of secondary alcohols, etc. Their preparation from saccharin, a cheap and readly available starting material, is simple.

The role of helices 5 and 6 on the human β1-adrenoceptor activation mechanism

The human β1-adrenoceptor (β1AR) is a G-protein-coupled receptor (GPCR) involved in sympathetic system regulation through agonist-induced activation. The conserved CWXP-motif in helix 6 (rotamer toggle switch) is one of the most important activation switches in Class A GPCRs. In order to investigate how the agonist binding disturbs this switch, we carried out molecular dynamics simulations of a hβ1AR model in the apo and R-noradrenaline-bound forms. The results show that the agonist binding changes the β1-angle distribution of Cys336, Trp337 and Phe341 residues and increases the helix 6 bending. Overall, we provide a functional hβ1AR model, showing how the rotamer toggle switch mechanism works at atomic level.