9 documents found, page 1 of 1
Artificial intelligence for prediction of biological activities and generation ...
Pereira, Tiago O.; Abbasi, Maryam; Oliveira, Rita I.; Guedes, Romina A.; Salvador, Jorge A. R.; Arrais, Joel P.In this work, we develop a method for generating targeted hit compounds by applying deep reinforcement learning and attention mechanisms to predict binding affinity against a biological target while considering stereochemical information. The novelty of this work is a deep model Predictor that can establish the relationship between chemical structures and their corresponding [Formula: see text] values. We thoro...
New Scaffolds of Proteasome Inhibitors: Boosting Anticancer Potential by Exploi...
Guedes, Romina A.; Grilo, Jorge H.; Carvalho, Andreia N.; Fernandes, Pedro M. P.; Ressurreição, Ana S.; Brito, Vanessa; Santos, Adriana O.Cancer is a complex multifactorial disease whose pathophysiology involves multiple metabolic pathways, including the ubiquitin-proteasome system, for which several proteasome inhibitors have already been approved for clinical use. However, the resistance to existing therapies and the occurrence of severe adverse effects is still a concern. The purpose of this study was the discovery of novel scaffolds of protea...
Disclosing the antitumour potential of the marine bromoditerpene sphaerococceno...
Alves, Celso; Silva, Joana; Afonso, Marta B; Guedes, Romina A.; Guedes, Rita C.; Alvariño, Rebeca; Pinteus, Susete; Gaspar, Helena; Goettert, Márcia I.Nature has revealed to be a key source of innovative anticancer drugs. This study evaluated the antitumour potential of the marine bromoditerpene sphaerococcenol A on different cancer cellular models. Dose-response analyses (0.1-100 µM; 24 h) were accomplished in eight different tumour cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-MEL-28). Deeper studies were conducted on MFC-7 cells, nam...
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development,...
Leonardo-Sousa, Carlota; Carvalho, Andreia Neves; Guedes, Romina A.; Fernandes, Pedro M. P.; Aniceto, Natália; Salvador, Jorge A. R.; Gama, Maria JoãoProteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therap...
Disclosing the antitumour potential of the marine bromoditerpene sphaerococceno...
Alves, Celso; Silva, Joana; Afonso, Marta B.; Guedes, Romina A.; Guedes, Rita C.; Alvariño, Rebeca; Pinteus, Susete; Gaspar, Helena; Goettert, Marcia I.Nature has revealed to be a key source of innovative anticancer drugs. This study evaluated the antitumour potential of the marine bromoditerpene sphaerococcenol A on different cancer cellular models. Dose-response analyses (0.1–100 μM; 24 h) were accomplished in eight different tumour cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-MEL-28). Deeper studies were conducted on MFC-7 cells, nam...
Bromoditerpenes from the red seaweed Sphaerococcus coronopifolius as potential ...
Alves, Celso; Silva, Joana; Pintéus, Susete; Guedes, Romina A.; Guedes, Rita C.; Alvariño, Rebeca; Freitas, Rafaela; Goettert, Márcia I.; Gaspar, HelenaSeaweeds are a great source of compounds with cytotoxic properties with the potential to be used as anticancer agents. This study evaluated the cytotoxic and proteasome inhibitory activities of 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, and bromosphaerol isolated from Sphaerococcus coronopifolius. The cytotoxicity was evaluated on malignant cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-...
Chemical Patterns of Proteasome Inhibitors: Lessons Learned from Two Decades of...
Guedes, Romina A.; Aniceto, Natália; Andrade, Marina A. P.; Salvador, Jorge A. R.; Guedes, Rita C.Drug discovery now faces a new challenge, where the availability of experimental data is no longer the limiting step, and instead, making sense of the data has gained a new level of importance, propelled by the extensive incorporation of cheminformatics and bioinformatics methodologies into the drug discovery and development pipeline. These enable, for example, the inference of structure-activity relationships ...
Computational Approaches for the Discovery of Human Proteasome Inhibitors: An O...
Guedes, Romina A.; Serra, Patrícia; Salvador, Jorge A. R.; Guedes, Rita C.Proteasome emerged as an important target in recent pharmacological research due to its pivotal role in degrading proteins in the cytoplasm and nucleus of eukaryotic cells, regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription, immune response, and signaling processes. The last two decades witnessed intensive efforts to discover 20S proteas...
3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: inhibition of ...
Carreiro, Elisabete P.; Louro, Patrícia; Adriano, Gizé; Guedes, Romina A.; Vannuchi, Nicholas; Costa, Ana R.; Antunes, Célia M. M.; Guedes, Rita C.Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihy...