37 documents found, page 1 of 4
Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity
Lopes, Elizabeth A.; Mestre, Raquel; Fontinha, Diana; Legac, Jenny; Pei, Jinxin V.; Sanches-Vaz, Margarida; Mori, Mattia; Lehane, Adele M.Malaria remains a prevalent infectious disease in developing countries. The first-line therapeutic options are based on combinations of fast-acting artemisinin derivatives and longer-acting synthetic drugs. However, the emergence of resistance to these first-line treatments represents a serious risk, and the discovery of new effective drugs is urgently required. For this reason, new antimalarial chemotypes with...
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...
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...
Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents ...
Espadinha, Margarida; Barcherini, Valentina; Gonçalves, Lídia; Molins, Elies; Antunes, Alexandra M. M.; Santos, Maria M. M.Gastric cancer is one of the deadliest cancers in modern societies, so there is a high level of interest in discovering new drugs for this malignancy. Previously, we demonstrated the ability of tryptophanol-derived polycyclic compounds to activate the tumor suppressor protein p53, a relevant therapeutic target in cancer. In this work, we developed a novel series of enantiomerically pure tryptophanol-derived sma...
SLMP53-1 Inhibits Tumor Cell Growth through Regulation of Glucose Metabolism an...
Ramos, Helena; Calheiros, Juliana; Almeida, Joana; Barcherini, Valentina; Santos, Sónia; Carvalho, Alexandra T. P.; Santos, Maria M. M.The Warburg effect is an emerging hallmark of cancer, which has the tumor suppressor p53 as its major regulator. Herein, we unveiled that p53 activation by (S)-tryptophanol-derived oxazoloisoindolinone (SLMP53-1) mediated the reprograming of glucose metabolism in cancer cells and xenograft human tumor tissue, interfering with angiogenesis and migration. Particularly, we showed that SLMP53-1 regulated glycolysis...
SLMP53-1 interacts with wild-type and mutant p53 DNA-binding domain and reactiv...
Gomes, A. S.; Ramos, Helena; Gomes, S.; Loureiro, Joana B.; Soares, Joana; Barcherini, Valentina; Monti, Paola; Fronza, GilbertoBackground Half of human cancers harbour TP53 mutations that render p53 inactive as a tumor suppressor. As such, reactivation of mutant (mut)p53 through restoration of wild-type (wt)-like function represents one of the most promising therapeutic strategies in cancer treatment. Recently, we have reported the (S)-tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a new reactivator of wt and mutp53 R280K with i...
Identification of tetracyclic lactams as NMDA receptor antagonists with potenti...
Espadinha, Margarida; Viejo, Lucía; Lopes, Ricardo M. R. M.; Herrera-Arozamena, Clara; Molins, Elies; Santos, Daniel J. V. A. dos; Gonçalves, LídiaN-Methyl-d-aspartate receptors (NMDARs) are crucial for the normal function of the central nervous system (CNS), and fundamental in memory and learning-related processes. The overactivation of these receptors is associated with numerous neurodegenerative and psychiatric disorders. Therefore, NMDAR is considered a relevant therapeutic target for many CNS disorders. Herein, we report the synthesis and pharmacolog...
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...
DIMP53-1: a novel small-molecule dual inhibitor of p53-MDM2/X interactions with...
Soares, Joana; Espadinha, Margarida; Raimundo, Liliana; Ramos, Helena; Gomes, Ana Sara; Gomes, Sara; Loureiro, Joana B.; Inga, Alberto; Reis, FlávioThe transcription factor p53 plays a crucial role in cancer development and dissemination, and thus, p53-targeted therapies are among the most encouraging anticancer strategies. In human cancers with wild-type (wt) p53, its inactivation by interaction with murine double minute (MDM)2 and MDMX is a common event. Simultaneous inhibition of the p53 interaction with both MDMs is crucial to restore the tumor suppres...