496858-32-3Relevant academic research and scientific papers
A novel atypical retinoid endowed with proapoptotic and antitumor activity
Cincinelli, Raffaella,Dallavalle, Sabrina,Merlini, Lucio,Penco, Sergio,Pisano, Claudio,Carminati, Paolo,Giannini, Giuseppe,Vesci, Loredana,Gaetano, Carlo,Illy, Barbara,Zuco, Valentina,Supino, Rosanna,Zunino, Franco
, p. 909 - 912 (2003)
The novel atypical retinoid E-3-(4′-hydroxy-3′-adamantylbiphenyl-4-yl)acrylic acid (ST1926, 4) exhibited a potent antiproliferative activity on a large panel of human tumor cells. Despite almost complete loss of ability to activate RARs, the compound was an effective apoptosis inducer and surprisingly produced DNA damage, that likely contributes to the proapoptotic activity. Following oral administration, 4 was well tolerated and caused tumor growth inhibition in the ovarian carcinoma, A2780/DX, and in the human melanoma, MeWo, growing in nude mice, thus supporting the therapeutic interest of the novel agent.
Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors
Cincinelli, Raffaella,Musso, Loana,Giannini, Giuseppe,Zuco, Valentina,De Cesare, Michelandrea,Zunino, Franco,Dallavalle, Sabrina
, p. 251 - 259 (2014/05/06)
To investigate the influence of the adamantyl group on the biological properties of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds having the adamantyl moiety in the cap structure were synthesized and compared to the corresponding hydroxamic acids lacking this group. An unexpected finding was the substantial reduction of inhibitory activity toward the tested enzymes, in particular HDAC6, following the introduction of the adamantyl group. In spite of the reduced ability to function as HDAC inhibitors, the compounds containing the adamantyl moiety still retained a good efficacy as antiproliferative and proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an appreciable antitumor activity against the colon carcinoma xenograft HCT116.
Synthesis and structure-activity relationships of a new series of retinoid-related biphenyl-4-ylacrylic acids endowed with antiproliferative and proapoptotic activity
Cincinelli, Raffaella,Dallavalle, Sabrina,Nannei, Raffaella,Carella, Serena,De Zani, Daniele,Merlini, Lucio,Penco, Sergio,Garattini, Enrico,Giannini, Giuseppe,Pisano, Claudio,Vesci, Loredana,Carminati, Paolo,Zuco, Valentina,Zanchi, Chiara,Zunino, Franco
, p. 4931 - 4946 (2007/10/03)
Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4′-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3′ (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 μM. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3′-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3′-adamantan-1-yl-4′- hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.
