Duvelisib (Copiktra®) is a dual inhibitor of phosphoinositide 3-kinases (PI3Kδ and PI3Kγ). In 2018, duvelisib was first approved by the Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma (SLL) after at least two prior therapies. Duvelisib has also been approved under accelerated track for relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. In this review, we provide a series of information about duvelisib, such as the development of clinical trials for LLC/SLL and FL and the steps used for its synthesis.

Despite the applicability of histone deacetylase inhibitors (HDACis) for cancer treatment, several works in the literature have shown that these inhibitors can be used in several other diseases, such as neurodegenerative diseases (NDs). This review begins by discussing the signaling pathways of HDACs, focused on the context of NDs, presenting a discussion about the pharmacophoric features of HDACis and crystal structure analysis and discussing interesting case studies from the literature about the development of HDACis. Additionally, a discussion about the consequences of isoform-selective inhibition vs pan-HDACis on neurotoxic effects and clinical trial investigations of HDACis for NDs is also presented.

Targeting histone deacetylases (HDACs) and phosphatidylinositol 3‐kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N‐acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.

Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. It has been shown that lysine residues play a key role in the formation of these aggregates. Thus, the ability to disrupt aggregate formation by covalently modifying lysine residues could lead to the discovery of therapeutically relevant antiamyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aβ as model amyloidogenic proteins, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation. We also observed that IQ reacted with free amines within the amyloid fibrils preventing their dissociation and seeding capacity.

Abstract:The possibility of obtaining new C-C bonds from the transition metals mediated catalysis, has represented a major advance in Organic Synthesis and correlated areas such as Chemistry of Natural Products and Medicinal Chemistry, since synthetically unreachable molecules could be obtained in an efficient and chemosselective way, from simple reactants. The cross-coupling reactions, as some of these processes are called, have gained prominence since the original publications of Suzuki-Miyaura, Kumada-Tamao-Corriu, Mizoroki-Heck, Sonogashira, Stille -during the 1970's -and Hiyama -in 1988. Since then numerous efforts are made by scientists around the world in order to not only understand better these processes, but also develop new catalytic systems with more efficiency and applicable to a wider range of substrates and the concepts of Green Chemistry. This work aims to expose some of the advances published by scientists around the world, in the last six years, based on this theme.Keywords: Cross coupling; new substrates; microwaves; palladium; gold. ResumoA possibilidade de se obter novas ligações C-C, a partir de reações de catálise mediadas por metais de transição, tem representado um grande avanço em Síntese Orgânica e áreas correlatas como a Química de Produtos Naturais e a Química Medicinal, uma vez que moléculas até então inalcançáveis sinteticamente puderam ser obtidas de forma eficiente e quimiosseletiva a partir de reagentes simples. As reações de acoplamento cruzado, como alguns desses processos são chamados, têm ganhado destaque desde as publicações originais de Suzuki-Miyaura, Kumada-Tamao-Corriu, Mizoroki-Heck, Sonogashira, Stille -durante a década de 1970 -e de Hiyama -em 1988. Desde então são numerosos os esforços feitos por cientistas do mundo todo no sentido de não apenas entender melhor tais processos, mas também desenvolver novos sistemas catalíticos mais eficientes e aplicáveis a uma maior variedade de substratos e aos conceitos da Química Verde. Este trabalho objetiva expor alguns dos avanços publicados por cientistas ao redor do mundo, nos últimos seis anos, com base neste tema.