Liquid chromatography enantioseparation and determination of enantiomeric purity of synthetized xanthone and benzophenone derivatives comprising one or more chiral moieties are reported. High enantioselectivity and resolution were observed in (S,S)‐Whelk‐O1 chiral stationary phase (CSP) for the enantiomeric mixtures of compounds comprising an aromatic ring linked to the stereogenic center(s), with α values ranging from 1.35 to 4.15 and Rs values ranging from 2.22 to 13.87. Among all the tested enantiomeric mixtures, those comprising three chiral moieties positioned in the xanthone scaffold gave the best chromatographic results. Enantiomers comprising an alkyl chain linked to the stereogenic centers were enantioseparated on a Lux® Celullose‐2 CSP. For both CSPs, the elution was performed in polar organic mode. The enantiomeric ratio (e.r.) values were always higher than 99%. Additionally, assessment of chiral recognition mechanisms on (S,S)‐Whelk‐O1 CSP was performed by molecular docking approach, which are in accordance with the chromatographic parameters. The nature and number of chiral moieties in the central aromatic scaffold of either xanthone or benzophenone derivatives are proved to be crucial for enantiorecognition. The evaluation of the growth inhibition of human tumor cell lines revealed that (S,S)‐(+)‐5 was the most potent compound, with values of GI₅₀ of 12.83 ± 2.09 μM for A375‐C5 melanoma, 12.40 ± 1.16 μM for MCF‐7 breast adenocarcinoma, and 13.06 ± 1.29 μM for NCI‐H460 non‐small cell lung cancer. In some cases, the growth inhibitory effects demonstrated to be dependent on the stereochemistry of the compounds.

中文翻译：

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氧杂蒽酮和二苯甲酮的手性衍生物：合成、对映分离、分子对接和肿瘤细胞生长抑制研究

报道了合成的包含一个或多个手性部分的呫吨酮和二苯甲酮衍生物的液相色谱对映体分离和对映体纯度的测定。在 ( S , S )-Whelk-O1 手性固定相 (CSP)中观察到高对映选择性和分辨率，对于包含连接到立体中心的芳香环的化合物的对映异构混合物，α 值范围为 1.35 至 4.15 和卢比值范围从 2.22 到 13.87。在所有测试的对映异构体混合物中，包含位于呫吨酮支架中的三个手性部分的那些得到最好的色谱结果。包含与立体中心连接的烷基链的对映异构体在 Lux® Celullose-2 CSP 上进行对映分离。对于这两种 CSP，洗脱都是在极性有机模式下进行的。对映体比率 (er) 值始终高于 99%。此外，对 ( S , S)-Whelk-O1 CSP 通过分子对接方法进行，符合色谱参数。氧杂蒽酮或二苯甲酮衍生物的中心芳香支架中手性部分的性质和数量被证明对于对映识别至关重要。对人肿瘤细胞系生长抑制的评估表明，( S,S )-(+)- 5是最有效的化合物，A375-C5 黑色素瘤的 GI ₅₀值为 12.83 ± 2.09 μM，12.40 ± 1.16 μM对于 MCF-7 乳腺癌，NCI-H460 非小细胞肺癌为 13.06 ± 1.29 μM。在某些情况下，生长抑制作用被证明取决于化合物的立体化学。