Shakil Md Salman, Parveen Shahida, Rana Zohaib, Walsh Fearghal, Movassaghi Sanam, Söhnel Tilo, Azam Mayur, Shaheen Muhammad Ashraf, Jamieson Stephen M F, Hanif Muhammad, Rosengren Rhonda J, Hartinger Christian G
Department of Pharmacology and Toxicology, University of Otago, PO Box 56, Dunedin 9016, New Zealand.
School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Biomedicines. 2021 Jan 27;9(2):123. doi: 10.3390/biomedicines9020123.
Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones - and 3-hydroxy-4-thiopyridones - as well as their Ru(η--cymene)Cl complexes -, and report here the molecular structures of and as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones -, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low μM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.
羟基吡啶酮是一类在药学上很重要的化合物，已在药物研发的多个领域展现出潜力。我们研究了3-羟基-4-吡啶酮和3-羟基-4-硫代吡啶酮，以及它们的Ru(η⁶-对异丙基苯)Cl配合物，并在此报告通过X射线衍射分析确定的[具体化合物1]和[具体化合物2]的分子结构。详细的细胞生物学研究揭示了其强大的细胞毒性活性，特别是3-羟基-4-硫代吡啶酮的活性，而这两种化合物类型的Ru配合物活性较弱，尽管在低 microM范围内仍显示出抗增殖活性。这些化合物没有调节癌细胞的细胞周期分布，但对癌细胞有其他影响，在A549细胞中具有细胞生长抑制作用，在NCI-H522非小细胞肺癌细胞中具有细胞毒性。
