1803612-14-7Relevant academic research and scientific papers
Novel adamantyl retinoid-related molecules with POLA1 inhibitory activity
Cardile, Francesco,Cincinelli, Raffaella,Colelli, Fabiana,Dallavalle, Sabrina,Darwiche, Nadine,Fucci, Alessandra,Gervasoni, Silvia,Guglielmi, Mario B.,La Porta, Ilaria,Luca D'Andrea, Egildo,Musso, Loana,Pisano, Claudio,Signorino, Giacomo,Vistoli, Giulio
, (2020)
Atypical retinoids (AR) or retinoid-related molecules (RRMs) represent a promising class of antitumor compounds. Among AR, E-3-(3′-adamantan-1-yl-4′-hydroxybiphenyl-4-yl)acrylic acid (adarotene), has been extensively investigated. In the present work we report the results of our efforts to develop new adarotene-related atypical retinoids endowed also with POLA1 inhibitory activity. The effects of the synthesized compounds on cell growth were determined on a panel of human and hematological cancer cell lines. The most promising compounds showed antitumor activity against several tumor histotypes and increased cytotoxic activity against an adarotene-resistant cell line, compared to the parent molecule. The antitumor activity of a selected compound was evaluated on HT-29 human colon carcinoma and human mesothelioma (MM487) xenografts. Particularly significant was the in vivo activity of the compound as a single agent compared to adarotene and cisplatin, against pleural mesothelioma MM487. No reduction of mice body weight was observed, thus suggesting a higher tolerability with respect to the parent compound adarotene.
