Derivatization of Rosmarinic Acid Enhances its in vitro Antitumor, Antimicrobial and Antiprotozoal Properties.

Silvia Bittner Fialová,Lívia Slobodníková,Miloš Lukáč,Mária Garajová,Vlastimil Zachar,Ivana Holková,Martin Mrva,Martin Kello,Eva Drobná,Matúš Čoma

doi:10.3390/molecules24061078

Silvia Bittner Fialová, Lívia Slobodníková + Show 8 more

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https://doi.org/10.3390/molecules24061078

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Abstract

On its own, rosmarinic acid possesses multiple biological activities such as anti-inflammatory, antimicrobial, cardioprotective and antitumor properties, and these are the consequence of its ROS scavenging and inhibitory effect on inflammation. In this study, two quaternary phosphonium salts of rosmarinic acid were prepared for the purpose of increasing its penetration into biological systems with the aim of improving its antimicrobial, antifungal, antiprotozoal and antitumor activity. The synthetized molecules, the triphenylphosphonium and tricyclohexylphosphonium salts of rosmarinic acid, exhibited significantly stronger inhibitory effects on the growth of HCT116 cells with IC50 values of 7.28 or 8.13 μM in comparison to the initial substance, rosmarinic acid (>300 μM). For the synthesized derivatives, we detected a greater than three-fold increase of activity against Acanthamoeba quina, and a greater than eight-fold increase of activity against A. lugdunensis in comparison to rosmarinic acid. Furthermore, we recorded significantly higher antimicrobial activity of the synthetized derivatives when compared to rosmarinic acid itself. Both synthetized quaternary phosphonium salts of rosmarinic acid appear to be promising antitumor and antimicrobial agents, as well as impressive molecules for further research.

Highlights

Rosmarinic acid (RA), as an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, is an important naturally-occurring phenolic secondary metabolite
The synthesis of phosphonium salts derived from rosmarinic acid is depicted in Scheme 1
The compounds RAP1 and RAP2 exhibited the most significant inhibitory effects on the growth of HCT116 cells (Figure 1), with IC50 values of 7.28 and 8.13 μM, respectively

Summary

Introduction

Rosmarinic acid (RA), as an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, is an important naturally-occurring phenolic secondary metabolite. It has been described as a tannin-like compound and was first isolated in 1958 by the Italian chemists Scarpati and Oriente from the Molecules 2019, 24, 1078; doi:10.3390/molecules24061078 www.mdpi.com/journal/molecules. RA is one of the most frequently occurring caffeic acid derivatives in the plant kingdom. It is a typical secondary metabolite for Lamiaceae plants, occurring in the Nepetoidae subfamily, which includes genera like Mentha, Melissa, Salvia, Rosmarinus, Lycopus, Origanum, Thymus etc. The presence of RA in the Lamiaceae outside of the Nepetoideae subfamily has been reported in the genus Teucrium, Aegiphila, or Hymenopyramis

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