Caffeic Acid Phosphanium Derivatives: Potential Selective Antitumor, Antimicrobial and Antiprotozoal Agents

Abstract

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 IC₅₀ value of CAPs ranged from 0.9 to 8.5 μM while IC₅₀ 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 <i>Candida albicans</i> (MIC 13-57 μM). The anti-<i>Acanthamoeba</i> activity was studied against two pathogenic <i>Acanthamoeba</i> strains. In the case of <i>A. lugdunensis</i>, all CAPs revealed a stronger inhibitory effect (EC₅₀ 74-3125 μM) than CA (>10⁵ µM), while in <i>A. quina</i> strain, the higher inhibition was observed for three derivatives (EC₅₀ 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.