12 documents found, page 1 of 2
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...
Mechanism of antifungal activity by 5-aminoimidazole-4-carbohydrazonamide deriv...
Cerqueira, Fátima; Maia, Marta; Gabriel, Carla; Medeiros, R.; 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 (Z)-5-amino-N’-aryl-1-methyl-1H-imidazole-4-carbohydrazonamides (2h, 2k, 2l) that had previously demonstrated st...
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...
SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promisin...
Gomes, Sara; Bosco, Bartolomeo; Loureiro, Joana B.; Ramos, Helena; Raimundo, Liliana; Soares, Joana; Nazareth, Nair; Barcherini, ValentinaHalf of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mut...
SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promisin...
Gomes, Sara; Bosco, Bartolomeo; Loureiro, Joana B.; Ramos, Helena; Raimundo, Liliana; Soares, Joana; Nazareth, Nair; Barcherini, ValentinaHalf of human cancers harbor <i>TP53</i> mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds...
Discovery of a small-molecule protein kinase Cδ-selective activator with promis...
Bessa, Cláudia; Soares, Joana; Raimundo, Liliana; Loureiro, Joana B.; Gomes, Célia; Reis, Flávio; Soares, Miguel L.; Santos, Daniel; Dureja, ChetnaProtein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (R...