## 4 Polyphenols
### Phenolic Acids
#### 4.3.2 Hydroxycinnamic Acids  
Hydroxcinnamic acids (**54-58**) are described in Table 2. It should be noted that chlorogenic acid (**58**) is structurally related to caffeic acid (**55**). Compounds **54-57** feature the cinnamic acid core, with substitutions _meta_ and _para_ to the short chain, unsaturated carboxylic acid. Compound **54** features a single \(p\)-hydroxy. Compounds **55**, **56**, and **57** have \(m\)- and \(p\)-substitutions with **55** containing two hydroxy groups, **56** a \(m\)-methoxy and \(p\)-hydroxy, and **57** a \(m\)-hydroxy and \(p\)-methoxy. Compound **58** differs in that a quinic acid is linked via esterification of caffeic acid. The double bond of the propene side chain can alternate between the _cis_ and _trans_ positions under increased energetic conditions; however, the _trans_ configuration is more stable.  
\begin{table}
\begin{tabular}{c c c} \hline \hline \multicolumn{1}{c}{HO} & \multicolumn{1}{c}{\(R_{1}\)} & \multicolumn{1}{c}{\(R_{2}\)} \\ \hline \(p\)-Coumaric acid, **54** & H & OH \\ Caffeic acid, **55** & OH & OH \\ Ferulic acid, **56** & OMe & OH \\ Isoferulic, **57** & OH & OMe \\ \hline \hline \end{tabular}
\end{table}
Table 2: Structures of hydroxycinnamic acid derivatives (**54-58**). Quinic acid is highlighted in olive.  
When compared to hydroxybenzoic acids these compounds generally have a stronger antimicrobial activity [101]. This has been attributed to the propene side chain leading to the carboxylic acid. It is assumed that the increased lipophilicity of this structure makes it more suitable for penetrating bacterial membranes [104]. The addition of hydroxy and methoxy groups also reduces the antibacterial activity of these compounds, but less than observed with hydroxybenzoic acids [101].  
Transformation of cinnamic acid from _trans_- to _cis_-configuration raises a notable bactericidal and synergistic activity against multiple-drug resistant _Mycobacterium tuberculosis_[105]. The mechanism for antibacterial activity among these compounds is also well defined. Described as weak organic acids, these compounds' antimicrobial activity is strongly linked to their ability to diffuse across cell membranes, causing an acidification of the cytoplasm, which leads to cell death [103].  
Several of the MICs for compounds **47-58** have been reported for common pathogenic bacteria. In general, these compounds do not possess strong antibacterial activity, with MIC values typically above 500 \(\mathrm{\SIUnitSymbolMicro g}/\mathrm{mL}\)[101, 102]. Lower MIC values have been reported in some instances, such as **56** exhibiting an MIC value of 100 \(\mathrm{\SIUnitSymbolMicro g}/\mathrm{mL}\) for _E. coli_ and _P. aeruginosa_[104]. In addition, **58** (3-0-caffeoylquinic acid or chlorogenic acid) produced MIC values of 100 \(\mathrm{\SIUnitSymbolMicro g}/\mathrm{mL}\) for _S. aureus_ and _E. coli_ and 200 \(\mathrm{\SIUnitSymbolMicro g}/\mathrm{mL}\) for _S. enterica_ and _Vibrio parahaemolyticus_[106].  
Additional sources also indicate a synergistic effect when used in combination with established antibacterial drugs. Compounds **54-56** and **58** all exhibit an enhancement of antibacterial activity when paired with commonly used antibiotics [107, 108]. It was also suggested that this effect could be due to these compounds' ability to damage cell membranes and increase permeability of the antibiotics [108].