Department of Chemistry, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland.
Adolphe Merkle Institute, Chemin des Verdiers 4, 1700 Fribourg, Switzerland.
J Inorg Biochem. 2020 Aug;209:111122. doi: 10.1016/j.jinorgbio.2020.111122. Epub 2020 May 26.
A series of tricarbonyl manganese complexes bearing 4-ethynyl-2,2'-bipyridine and 5-ethynyl-1,10-phenanthroline α-diimine ligands were synthetized, characterized and conjugated to vitamin B, previously used as a vector for drug delivery, to take advantage of its water solubility and specificity toward cancer cells. The compounds act as photoactivatable carbon monoxide-releasing molecules rapidly liberating on average ca. 2.3 equivalents of CO upon photo-irradiation. Complexes and conjugates were tested for their anticancer effects, both in the dark and following photo-activation, against breast cancer MCF-7, lung carcinoma A549 and colon adenocarcinoma HT29 cell lines as well as immortalized human bronchial epithelial cells 16HBE14o- as the non-carcinogenic control. Our results indicate that the light-induced cytotoxicity these molecules can be attributed to both their released CO and to their CO-depleted metal fragments including liberated ligands.
一系列含有 4-乙炔基-2,2'-联吡啶和 5-乙炔基-1,10-菲咯啉α-二亚胺配体的三羰基锰配合物被合成、表征，并与维生素 B 连接，维生素 B 以前曾被用作药物输送的载体，以利用其水溶性和对癌细胞的特异性。这些化合物作为光活化的一氧化碳释放分子，在光照射下迅速释放约 2.3 当量的 CO。复合物和缀合物在黑暗中和光激活后都针对乳腺癌 MCF-7、肺癌 A549 和结肠腺癌 HT29 细胞系以及永生的人支气管上皮细胞 16HBE14o-进行了抗癌效果测试，后者作为非致癌对照。我们的结果表明，这些分子的光诱导细胞毒性既可以归因于它们释放的 CO，也可以归因于它们耗尽 CO 的金属片段，包括释放的配体。
