Bednarczyk-Cwynar Barbara, Leśków Anna, Szczuka Izabela, Zaprutko Lucjusz, Diakowska Dorota
Department of Organic Chemistry, Poznan University of Medical Science, Grunwaldzka 6, 60-780 Poznan, Poland.
Department of Basic Sciences, Wroclaw Medical University, Chalubinskiego 3, 50-368 Wroclaw, Poland.
Pharmaceuticals (Basel). 2023 May 14;16(5):746. doi: 10.3390/ph16050746.
This study aimed to synthesize four new semisynthetic derivatives of natural oleanolic acid (OA) and, based on an analysis of their cytotoxic and anti-proliferative effects against human MeWo and A375 melanoma cell lines, select those with anti-cancer potential. We also screened the treatment time with the concentration of all four derivatives. We synthesized oxime 2 and performed its acylation with carboxylic acids into new derivatives and according to the methods previously described. Colorimetric MTT and SRB assays were used to measure the anti-proliferative and cytotoxic activity of OA and its derivatives , , and against melanoma cells. Selected concentrations of OA, the derivatives, and different time periods of incubation were used in the study. The data were analyzed statistically. The present results revealed the possible anti-proliferative and cytotoxic potential of two selected OA derivatives and , on A375 and MeWo melanoma cells, especially at concentrations of 50 μM and 100 μM at 48 h of incubation ( < 0.05). Further studies will be necessary to analyze the proapoptotic and anti-cancer activities of and against skin and other cancer cells. The bromoacetoxyimine derivative () of OA morpholide turned out to be the most effective against the tested cancer cells.
本研究旨在合成四种新的天然齐墩果酸（OA）半合成衍生物，并基于对其针对人MeWo和A375黑色素瘤细胞系的细胞毒性和抗增殖作用的分析，筛选出具有抗癌潜力的衍生物。我们还针对所有四种衍生物的浓度筛选了处理时间。我们按照先前描述的方法合成了肟2，并将其与羧酸进行酰化反应生成新的衍生物 和 。采用比色MTT法和SRB法测定OA及其衍生物 、 、 和 对黑色素瘤细胞的抗增殖和细胞毒性活性。研究中使用了选定浓度的OA、衍生物以及不同的孵育时间段。对数据进行了统计学分析。目前的结果显示，两种选定的OA衍生物 和 对A375和MeWo黑色素瘤细胞具有潜在的抗增殖和细胞毒性潜力，尤其是在孵育48小时、浓度为50 μM和100 μM时（ < 0.05）。有必要进一步研究 和 对皮肤及其他癌细胞的促凋亡和抗癌活性。OA吗啉化物的溴乙酰氧基肟衍生物（）被证明对测试的癌细胞最有效。
