Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia.
Institute of Microbiology, Faculty of Medicine, Comenius University Bratislava, University Hospital in Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
Int J Mol Sci. 2024 Jan 18;25(2):1200. doi: 10.3390/ijms25021200.
Caffeic acid (CA) is one of the most abundant natural compounds present in plants and has a broad spectrum of beneficial pharmacological activities. However, in some cases, synthetic derivation of original molecules can expand their scope. This study focuses on the synthesis of caffeic acid phosphanium derivatives with the ambition of increasing their biological activities. Four caffeic acid phosphanium salts (CAPs) were synthesized and tested for their cytotoxic, antibacterial, antifungal, and amoebicidal activity in vitro, with the aim of identifying the best area for their medicinal use. CAPs exhibited significantly stronger cytotoxic activity against tested cell lines (HeLa, HCT116, MDA-MB-231 MCF-7, A2058, PANC-1, Jurkat) in comparison to caffeic acid. Focusing on Jurkat cells (human leukemic T cell lymphoma), the IC value of CAPs ranged from 0.9 to 8.5 μM while IC of CA was >300 μM. Antimicrobial testing also confirmed significantly higher activity of CAPs against selected microbes in comparison to CA, especially for Gram-positive bacteria (MIC 13-57 μM) and the yeast (MIC 13-57 μM). The anti- activity was studied against two pathogenic strains. In the case of , all CAPs revealed a stronger inhibitory effect (EC 74-3125 μM) than CA (>10 µM), while in strain, the higher inhibition was observed for three derivatives (EC 44-291 μM). The newly synthesized quaternary phosphanium salts of caffeic acid exhibited selective antitumor action and appeared to be promising antimicrobial agents for topical application, as well as potential molecules for further research.
咖啡酸（CA）是植物中含量最丰富的天然化合物之一，具有广泛的有益的药理活性。然而，在某些情况下，原始分子的合成衍生可以扩大其范围。本研究专注于合成咖啡酸膦盐衍生物，以提高其生物活性。合成了四种咖啡酸膦盐（CAP），并测试了它们的体外细胞毒性、抗菌、抗真菌和杀阿米巴活性，旨在确定其药用的最佳领域。与咖啡酸相比，CAP 对测试的细胞系（HeLa、HCT116、MDA-MB-231 MCF-7、A2058、PANC-1、Jurkat）表现出显著更强的细胞毒性活性。以 Jurkat 细胞（人白血病 T 细胞淋巴瘤）为例，CAP 的 IC 值范围为 0.9 至 8.5 μM，而 CA 的 IC 值>300 μM。抗菌测试还证实，与 CA 相比，CAP 对选定的微生物具有更高的活性，尤其是对革兰氏阳性菌（MIC 13-57 μM）和酵母（MIC 13-57 μM）。对两种致病性菌株进行了抗活性研究。在 菌株的情况下，所有 CAP 都显示出比 CA 更强的抑制作用（EC 74-3125 μM）（>10 µM），而在 菌株中，三种衍生物观察到更高的抑制作用（EC 44-291 μM）。新合成的咖啡酸季铵盐表现出选择性的抗肿瘤作用，并且似乎是局部应用有前途的抗菌剂，以及进一步研究的潜在分子。
