Three-Component Gold(I)-Catalyzed Alkoxyvinylation.

Acetylene has been underexploited despite being a highly valuable feedstock for chemical synthesis. We have developed the first true gold(I)-catalyzed intermolecular three-component reaction between acetylene, alkenes, and alcohols to afford ß-vinyl hemiaminal scaffolds from N-vinyl amides. Unusual biscyclopropyl and 3-vinyl N-heterocyclic scaffolds were obtained through the incorporation of a second N-vinyl unit or tethered alkene into the starting material.

Quality of Care in Pediatric Palliative Care: A Scoping Review.

Palliative care (PC) enhances the quality of life for patients and families facing life-threatening conditions. While PC is well-established for adults, not all practices apply to pediatrics. Consequently, specific quality indicators for Pediatric Palliative Care (PPC) must be identified. This scoping review aimed to identify the variables associated with the quality of care of PPC patients in Spain, focusing specifically on three areas: structure and process of care, psychological aspects of care, and care of patients approaching the end of life. The review was conducted following PRISMA-ScR guidelines. Searches were performed in the PubMed, Scopus, Web of Science, Embase, ProQuest, and Dialnet databases covering the period extending from January 2000 to May 2023. Finally, 35 studies were identified for the complete review. A total of 30 studies include variables associated with the structure and process of care, 20 include variables associated with psychological aspects of care, and 23 studies integrate variables related to patient care at the end of life. Analysis suggests that enhancing professional training in aspects such as communication with patients and families, creating intimate spaces with flexible visiting hours, increasing emotional support, promoting frequent contact with healthcare teams, and transparently communicating about illness and imminent death to both families and minors could improve the quality of PPC.

Gold(I)-Catalyzed Intermolecular Aryloxyvinylation with Acetylene Gas.

Acetylene gas is an important feedstock for chemical production, although it is underutilized in organic synthesis. We have developed an intermolecular gold(I)-catalyzed alkyne/alkene reaction of o-allylphenols with acetylene gas that gives rise to chromanes by a stereospecific aryloxycyclization through the nucleophilic regioselective opening of cyclopropyl gold(I)-carbene intermediates. The synthetic application of this method was demonstrated in the late-stage functionalization of the natural product lapachol.

Imidazoline- and Benzamidine-Based Trypanosome Alternative Oxidase Inhibitors: Synthesis and Structure-Activity Relationship Studies.

The trypanosome alternative oxidase (TAO), a mitochondrial enzyme involved in the respiration of the bloodstream form trypomastigotes of Trypanosoma brucei, is a validated drug target against African trypanosomes. Earlier series of TAO inhibitors having a 2,4-dihydroxy-6-methylbenzoic acid scaffold ("head") and a triphenylphosphonium or quinolin-1-ium cation as a mitochondrion-targeting group ("tail") were shown to be nanomolar inhibitors in enzymatic and cellular assays. We investigated here the effect of different mitochondrion-targeting cations and other scaffold modifications on the in vitro activity of this class of inhibitors. Low micromolar range activities were obtained, and the structure-activity relationship studies showed that modulation of the tail region with polar substituents is generally detrimental to the enzymatic and cellular activity of TAO inhibitors.

Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs.

Three neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(κ2-(C^N)Cl(L)], where C^N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = Bifonazole (BFZ) for [Pt-BFZ]). The complexes have been completely characterized in solution and the crystal structures of [Pt-BFZ] and [Pt-CTZ] have been resolved. Complexes [Pt-MeIm] and [Pt-BFZ] present higher cytotoxicity than cisplatin in SW480 (colon adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian cancer) cell lines. [Pt-MeIm] shows the highest accumulation in A549 cells, in agreement with its inability to interact with serum albumin. By contrast, [Pt-CTZ] and [Pt-BFZ] interact with serum proteins, a fact that reduces their bioavailability. The strongest interaction with bovine serum albumin (BSA) is found for [Pt-BFZ], which is the least internalized inside the cells. All the complexes are able to covalently interact with DNA. The most cytotoxic complexes, [Pt-MeIm] and [Pt-BFZ] induce cellular accumulation in G0/G1 and apoptosis by a similar pathway, probably involving a reactive oxygen species (ROS) generation mechanism. [Pt-BFZ] turns out to be the most efficient complex regarding ROS generation and causes mitochondrial membrane depolarization, whereas [Pt-MeIm] induces the opposite effect, hyperpolarization of the mitochondrial membrane. On the contrary, the least cytotoxic complex, [Pt-CTZ] cannot block the cell cycle or generate ROS and the mechanism by which it induces apoptosis could be a different one.

Pródromos de síndrome neuroléptica maligna associados ao uso de prometazina? Relato de caso / Promethazine administration associated neuroleptic malignant syndrome prodromi? Cae report

Relata-se um caso de síndrome neuroléptica maligna (SNM) cujas manifestações tiveram início após administração de prometazina. Sintomas atenuados antecederam em dias o quadro clínico completo, que se instalou totalmente no período inicial da internação hospitalar, cursando com evolução clínica favorável