29 documents found, page 1 of 3
A first-in-class inhibitor of homologous recombination DNA repair counteracts t...
Calheiros, Juliana; Silva, Rita; Barbosa, Filipa; Morais, João; Moura, Sara Reis; Almeida, Sofia; Fiorini, Elena; Mulhovo, Silva; Aguiar, Tatiana QuintaBackground Pancreatic ductal adenocarcinoma (PDAC) is among the cancer types with poorest prognosis and survival rates primarily due to resistance to standard-of-care therapies, including gemcitabine (GEM) and olaparib. Particularly, wild-type (wt)BRCA tumours, the most prevalent in PDAC, are more resistant to DNA-targeting agents like olaparib, restraining their clinical application. Recently, we disclosed a m...
Mechanistic Insights of a p53-Targeting Small Molecule
Ferreira, Ricardo J.F.; Barcherini, Valentina; Roma-Rodrigues, Catarina; Sikorová, Miriama; Saraiva, Lucília; Leandro, Ana P.; Baptista, Pedro V.Restoring the p53 pathway, particularly by reactivating wild-type (wt) or mutant (mut) p53, is considered a promising approach for cancer treatment. Previously, we identified the tryptophanol-derived oxazoloisoindolinone family as a new scaffold for obtaining wt and mut p53 reactivators. Herein, we report a detailed study on the pharmacokinetic profile and the mechanism of action of RVJB59, an (R)-tryptophanol-...
Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolys...
Bessa, Cláudia; Loureiro, Joana B.; Barros, Matilde; Isca, Vera M. S.; Sardão, Vilma A.; Oliveira, Paulo J.; Bernardino, Raquel L.Metabolic reprogramming is a central hub in tumor development and progression. Therefore, several efforts have been developed to find improved therapeutic approaches targeting cancer cell metabolism. Recently, we identified the 7a-acetoxy-6b-benzoyloxy-12-O-benzoylroyleanone (Roy- Bz) as a PKC -selective activator with potent anti-proliferative activity in colon cancer by stimulating a PKC -dependent mitochondr...
Targeting p53 for Melanoma Treatment: Counteracting Tumour Proliferation, Disse...
Loureiro, Joana B.; Raimundo, Liliana; Calheiros, Juliana; Carvalho, Carla; Barcherini, Valentina; Lima, Nuno R.; Gomes, Célia; Almeida, Maria InêsMelanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and...
A selective p53 activator and anticancer agent to improve colorectal cancer the...
Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Gomes, Célia; Reis, Flávio; Monteiro, Filipe A.; Nunes, CláudiaImpairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring W...
A selective p53 activator and anticancer agent to improve colorectal cancer the...
Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Gomes, Célia; Reis, Flávio; Monteiro, Filipe A; Nunes, CláudiaImpairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring W...
Targeting p53 for melanoma treatment: counteracting tumour proliferation, disse...
Loureiro, Joana B.; Raimundo, Liliana; Calheiros, Juliana; Carvalho, Carla; Barcherini, Valentina; Lima, Nuno R.; Gomes, Célia; Almeida, Maria InêsMelanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and...
Mechanism of Antifungal Activity by 5-Aminoimidazole-4-Carbohydrazonamide Deriv...
Cerqueira, Fátima; Maia, Marta; Gabriel, Carla; Medeiros, Rui; Cravo, Sara; Ribeiro, Ana Isabel; Dantas, Daniela; Dias, Alice Maria; Saraiva, LucíliaSystemic mycoses are one major cause of morbidity/mortality among immunocompromised/debilitated individuals. Studying the mechanism of action is a strategy to develop safer/potent antifungals, warning resistance emergence. The major goal of this study was to elucidate the mechanism of action of three (<i>Z</i>)-5-amino-<i>N</i>’-aryl-1-methyl-1<i>H</i>-imidazole-4-carbohydrazonamides (2h, 2k, 2l) that had previ...
A selective p53 activator and anticancer agent to improve colorectal cancer the...
Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Gomes, Célia; Reis, Flávio; Monteiro, Filipe A.; Nunes, CláudiaImpairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring W...
Semi-synthesis of small molecules of aminocarbazoles: tumor growth inhibition a...
Long, Solida; Loureiro, Joana B.; Carvalho, Carla; Gales, Luís; Saraiva, Lucília; Pinto, Madalena M. M.; Puthongking, Ploenthip; Sousa, EmíliaThe 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 (<...