Işilar Özer, Bulut Adnan, Tombul Mustafa, Güner Adem, Şahin Onur
Department of Chemistry, Faculty of Engineering and Natural Sciences, Kırıkkale University, Kırıkkale, Turkey.
Department of Occupational Health & Safety, Faculty of Health Sciences, Sinop University, Sinop, Turkey.
Future Med Chem. 2025 May;17(9):991-997. doi: 10.1080/17568919.2025.2504328. Epub 2025 May 14.
The principal objective of the conducted study is to synthesize enantiomerically pure a class of sugar-based (thio)ureas (9-12) and to investigate their antiproliferative activities against the A549 (lung cancer), MCF-7 (breast cancer), and PANC1 (human pancreatic cancer) cell lines.
The synthesis of (thio)urea sugars was performed by two stage procedure. First, the amino sugars (4 and 8) were obtained in three steps (tosylation, substitution and reduction). And secondly, the reaction of 3,5-bis(trifluoromethyl)phenyliso(thio)cyanate with the corresponding amines gave chiral (thio)urea derivatives (9-12). Cell viability was determined in human A549, MCF-7, PANC-1 and noncancer human embryonic kidney (HEK-293) cell lines.
Four chiral sugar (thio)ureas (9-12) were synthesized and screened against the A549, MCF-7, and PANC1 cell lines. Of the four chiral sugar derivatives, the compound 9 not only showed the best anticancer activity in the A549 cell line but also provided the highest normal cell (HEK-293) viability.
From chiral sugar-derived (thio)ureas obtained, the compound 9 was found to be shown the highest activity against A549 cancer cell line. The compound 9, therefore, gave more promising results for future researches as anti-cancer agents. X-ray studies revealed that amide type hydrogens are playing important roles in anti-cancer activities.
本研究的主要目的是合成一类对映体纯的糖基（硫）脲（9 - 12），并研究它们对A549（肺癌）、MCF - 7（乳腺癌）和PANC1（人胰腺癌）细胞系的抗增殖活性。
（硫）脲糖的合成采用两步法。首先，通过三步反应（甲苯磺酰化、取代和还原）得到氨基糖（4和8）。其次，3,5 - 双（三氟甲基）苯基异（硫）氰酸酯与相应的胺反应得到手性（硫）脲衍生物（9 - 12）。在人A549、MCF - 7、PANC - 1和非癌人胚肾（HEK - 293）细胞系中测定细胞活力。
合成了四种手性糖（硫）脲（9 - 12），并针对A549、MCF - 7和PANC1细胞系进行筛选。在这四种手性糖衍生物中，化合物9不仅在A549细胞系中表现出最佳的抗癌活性，而且对正常细胞（HEK - 293）的活力影响最小。
在所得到的手性糖衍生的（硫）脲中，发现化合物9对A549癌细胞系具有最高活性。因此，化合物9作为抗癌药物在未来研究中显示出更有前景的结果。X射线研究表明，酰胺型氢在抗癌活性中起重要作用。
