11 documents found, page 1 of 2
Semi-synthesis of small molecules of aminocarbazoles: Tumor growth inhibition a...
Long, S; Loureiro, JB; Carvalho, C; Gales, L; Saraiva, L; Pinto, MMM; Puthongking, P; Sousa, EThe tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1...
Tetracyclic thioxanthene derivatives: Studies on fluorescence and antitumor act...
Durães, F; Silva, PMA; Novais, P; Amorim, I; Gales, L; Esteves, CIC; Guieu, S; Bousbaa, H; Pinto, M; Sousa, EThioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline– chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375...
Determination of the absolute configuration of bioactive indole-containing pyra...
Long, S; Furlani, IL; Oliveira, JM; Resende, DISP; Silva, AMS; Gales, L; Pereira, JA; Kijjoa, A; Cass, QB; Oliveira, RV; Sousa, E; Pinto, MMMIn recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H...
Antimicrobial activity of a library of thioxanthones and their potential as eff...
Durães, F; Palmeira, A; Cruz, B; Freitas-Silva, J; Szemerédi, N; Gales, L; Costa, PM; Remião, F; Silva, R; Pinto, M; Spengler, G; Sousa, EThe overexpression of efflux pumps is one of the causes of multidrug resistance, which leads to the inefficacy of drugs. This plays a pivotal role in antimicrobial resistance, and the most notable pumps are the AcrAB-TolC system (AcrB belongs to the resistance-nodulation-division family) and the NorA, from the major facilitator superfamily. In bacteria, these structures can also favor virulence and adaptation m...
Synthesis of a small library of nature-inspired xanthones and study of their an...
Resende, DISP; Pereira-Terra, P; Moreira, J; Freitas-Silva, J; Lemos, A; Gales, L; Pinto, E; Sousa, ME; Costa, PM; Pinto, MMMA series of thirteen xanthones 3-15 was prepared based on substitutional (appendage) diversity reactions. The series was structurally characterized based on their spectral data and HRMS, and the structures of xanthone derivatives 1, 7, and 8 were determined by single-crystal X-ray diffraction. This series, along with an in-house series of aminated xanthones 16-33, was tested for in-vitro antimicrobial activity ...
Repurposing benzbromarone for familial amyloid polyneuropathy: A new transthyre...
Cotrina, EY; Oliveira, Â; Leite, JP; Llop, J; Gales, L; Quintana, J; Cardoso, I; Arsequell, GTransthyretin (TTR) is a homotetrameric protein involved in human amyloidosis, including familial amyloid polyneuropathy (FAP). Discovering small-molecule stabilizers of the TTR tetramer is a therapeutic strategy for these diseases. Tafamidis, the only approved drug for FAP treatment, is not effective for all patients. Herein, we discovered that benzbromarone (BBM), a uricosuric drug, is an effective TTR stabil...
Tegsedi (Inotersen): An antisense oligonucleotide approved for the treatment of...
Gales, LTegsedi (Inotersen) is a chemicallymodified antisense oligonucleotide that inhibits the hepatic production of transthyretin (TTR). Several single-point mutations in TTR destabilize its structure, leading to the aggregation and accumulation of amyloid deposits in the nervous system, heart, kidneys and eyes. In July 2018, Tegsedi was approved by the European Commission for use in adults with stage one and two pol...
Comparative genomics reveals a novel genetic organization of the sad cluster in...
Reis, AC; Kolvenbach, BA; Chami, M; Gales, L; Egas, C; Corvini, PFX; Nunes, OCBACKGROUND: Microbial communities recurrently establish metabolic associations resulting in increased fitness and ability to perform complex tasks, such as xenobiotic degradation. In a previous study, we have described a sulfonamide-degrading consortium consisting of a novel low-abundant actinobacterium, named strain GP, and Achromobacter denitrificans PR1. However, we found that strain GP was unable to grow in...
Erubescensoic Acid, a new polyketide and a xanthonopyrone SPF-3059-26 From the ...
Kumla, D; Dethoup, T; Gales, L; Pereira, J; Freitas-Silva, J; Costa, P; Silva, A; Pinto, M; Kijjoa, AA new polyketide erubescensoic acid (1), and the previously reported xanthonopyrone, SPF-3059-26 (2), were isolated from the uninvestigated fractions of the ethyl acetate crude extract of the marine sponge-associated fungus Penicillium erubescens KUFA0220. The structures of the new compound, erubescensoic acid (1), and the previously reported SPF-3059-26 (2), were elucidated by extensive analysis of 1D and 2D-N...
The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328)...
Pereira, SB; Santos, M; Leite, JP; Flores, C; Eisfeld, C; Büttel, Z; Mota, R; Rossi, F; Philippis, R; Gales, L; Morais-Cabral, JH; Tamagnini, PMany cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications. However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species. In this work, genes putatively relate...