6 documents found, page 1 of 1
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...
Targeting p53 for melanoma treatment: Counteracting tumour proliferation, disse...
Loureiro, JB; Raimundo, L; Calheiros, J; Carvalho, C; Barcherini, V; Lima, NR; Gomes, C; Almeida, MI; Alves, MG; Costa, JL; Santos, MMM; Saraiva, LMelanoma 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, H; Soares, MIL; Silva, J; Raimundo, L; Calheiros, J; Gomes, C; Reis, F; Monteiro, FA; Nunes, C; Reis, S; Bosco, B; Piazza, S; Domingues, LImpairment 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...
Design and synthesis of new inhibitors of p53–MDM2 interaction with a chalcone ...
Pereira, D; Lima, RT; Palmeira, A; Seca, H; Soares, J; Gomes, S; Raimundo, L; Maciel, C; Pinto, M; Sousa, E; Vasconcelos, MH; Saraiva, L; Cidade, HThe virtual screening of a library of chalcone derivatives led us to the identification of potential new MDM2 ligands. The chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two chalcone...
SLMP53-2 restores wild-type-like function to mutant p53 through hsp70: Promisin...
Gomes, S; Bosco, B; Loureiro, JB; Ramos, H; Raimundo, L; Soares, J; Nazareth, N; Barcherini, V; Domingues, L; Oliveira, C; Bisio, A; Piazza, SHalf 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...
Discovery of a small-molecule protein kinase Cd-selective activator with promis...
Bessa, C; Soares, J; Raimundo, L; Loureiro, J; Gomes, C; Reis, F; Soares, ML; Santos, D; Dureja, C; Chaudhuri, S; Lopez-Haber, C; Kazanietz, MProtein 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 PKCd-selective activator, the 7a-acetoxy-6ß-benzoyloxy-12-O-benzoylroyleanone (R...