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.

非典型类维生素A（AR）或类维生素A相关分子（RRM）代表了有前途的一类抗肿瘤化合物。在AR中，已经广泛地研究了E -3-（3'-金刚烷-1-基-4'-羟基联苯-4-基）丙烯酸（金刚烷）。在目前的工作中，我们报告了我们努力开发新的与胡萝卜素相关的非典型类维生素A（也具有POLA1抑制活性）的结果。在一组人类和血液癌细胞系中确定了合成化合物对细胞生长的影响。与母体分子相比，最有前途的化合物显示出对几种肿瘤组织型的抗肿瘤活性，并增强了对抗金刚烷抗性细胞系的细胞毒性活性。

评价所选化合物对HT-29人结肠癌和人间皮瘤（MM487）异种移植物的抗肿瘤活性。与金刚烷和顺铂相比，该化合物作为单一药物的体内活性对胸膜间皮瘤MM487的体内活性尤为重要。没有观察到小鼠体重的减少，因此表明相对于母体化合物金刚烷烃更高的耐受性。