Caffeic Acid Phosphanium Derivatives: Potential Selective Antitumor, Antimicrobial and Antiprotozoal Agents
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Published:2024-01-18
Issue:2
Volume:25
Page:1200
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Lukáč Miloš1, Slobodníková Lívia2, Mrva Martin3, Dušeková Aneta3, Garajová Mária3, Kello Martin4ORCID, Šebová Dominika4, Pisárčik Martin1, Kojnok Marián1, Vrták Andrej1, Kurin Elena5, Bittner Fialová Silvia5ORCID
Affiliation:
1. Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia 2. Institute of Microbiology, Faculty of Medicine, Comenius University Bratislava, University Hospital in Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia 3. Department of Zoology, Faculty of Natural Sciences, Comenius University Bratislava, Mlynská Dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia 4. Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Trieda SNP 1, 040 11 Košice, Slovakia 5. Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia
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 Candida albicans (MIC 13–57 μM). The anti-Acanthamoeba activity was studied against two pathogenic Acanthamoeba strains. In the case of A. lugdunensis, all CAPs revealed a stronger inhibitory effect (EC50 74–3125 μM) than CA (>105 µM), while in A. quina 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.
Funder
Grant Agency of the Ministry of Education, Science, Research, and Sport of Slovakia Slovak Research and Development Agency
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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