PRC2 allosteric modulation an alternative strategy in drug discovery for the epigenetic diseases

Synthesis and antirpoliferative activity of isoxazolo[3,4-d]pyridazin-7(6H)-one derivatives

3,4-diphenylisoxazolo[3,4-d]pyridazin-7(6H)-one analogs were synthesized and tested for the antiproliferative activity. Study on the cell cycle alteration and on some cellular target (ATM, procaspase-2 proteins and H2AX histone) demonstrate the increase of the cell population in S phase and to induce cellular death by apoptosis by DNA damage with double strand breaks.

Role of hypoxia in pemetrexed-resistance of mesothelioma mediated by proton-coupled folate transporter, and preclinical activity of new anti-LDH compounds

Introduction There are few effective therapies for malignant pleural mesothelioma (MPM), which remains one of the most lethal cancers. We previously demonstrated that low expression of the PCFT transporter, both at mRNA and protein levels, is associated with shorter survival of MPM patients treated with pemetrexed (Giovannetti et al., 2017). Since hypoxia has also been associated to antifolate-resistance (Raz et al, 2014), this study was aimed at elucidating key factors in pemetrexed resistance and hypoxia that may contribute to the rational development of novel therapeutic interventions against mesothelioma. Methods The levels of PCFT and of the hypoxia marker carbonic anhydrase-IX were de…

NUOVI DERIVATI 2-ACETAMMIDOBENZAMMIDICI: ATTIVITÀ ANTIPROLIFERATIVA E POSSIBILE MECCANISMO DI AZIONE

Le cinnammido benzammidi rappresentano una classe di sostanze biologicamente attive di grande interesse farmaceutico. Nonostante siano state descritte per svariate attività biologiche, nessun dato è stato riportato sulla loro attivita antitumorale. Inizialmente una serie di 2-cinammidobenzammidi variamente sostituite sono state sintetizzate e valutate per la loro attività antiproliferativa. Partendo dal derivato risultato più attivo, il 2-cinnammido-5-iodobenzammide, che ha mostrato una percentuale di inibizione della crescita sulle K562 del 74% a 10μM, sono stati sintetizzati una serie di derivati al fine di approfondirne la SAR.I composti così ottenuti sono risultati attivi nei confronti …

CCDC 644638: Experimental Crystal Structure Determination

Related Article: D.Raffa, B.Maggio, S.Cascioferro, M.V.Raimondi, D.Schillaci, G.Gallo, G.Daidone, S.Plescia, F.Meneghetti, G.Bombieri, A.Di Cristina, R.M.Pipitone, S.Grimaudo, M.Tolomeo|2009|Eur.J.Med.Chem.|44|165|doi:10.1016/j.ejmech.2008.03.023