1. Introduction
Gaultheria procumbens L (Wintergreen) is a small ericaceous plant cultivated for use in the landscape industry, and it is the source of the essential oil from wintergreen (WO) [
1,
2]. WO is obtained commercially by steam distillation; however, the most commonly used form of WO is synthetic. Wintergreen oil is now commonly used as a flavoring agent, but its leaves were historically used by North American natives for the treatment of aches and pains because of their analgesic activity. In fact, MS, the most common salicylate in commercial wintergreen preparations, is routinely used in topical ointments for the treatment of inflammation [
2]. It has been demonstrated that some plants produce salicylic acid (SA) as a response to the infection by tobacco mosaic virus (TMV) [
3]. Neighboring plants also develop resistance to TMV because the infected plants convert the SA to MS, which, being more volatile, is released into the air and signals the neighboring plants to increase their resistance to TMV.
Oloyede [
4] demonstrated the antimicrobial activity of the essential oil from
Laportea aestuans (Gaud). The principal constituents in the oil were MS (54.50%), fenchol (10.59%), 1,2-cyclohexanedione dioxime (9.40%), 1,4-octadiene (8.86%) and linalool (3.26%). The oil exhibited activity against
Escherichia coli, Staphylococcus aureus (S. aureus), Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Candida albicans, Rhizopus stolon, Aspergillus niger and Penicillium nonatum.
MS can be ingested from various sources, including chewing gum, baked goods, syrups, candy, beverages, ice cream, and tobacco products. A review of the literature regarding the toxicity of MS when ingested orally arrived at an allowable daily intake of 11 mg/kg/d [
5]. Vlachojannis et al. [
6] explored the antimicrobial activity of Listerine, which is a popular mouthwash that contains MS as one of its components. In the past century, its recipe was changed from an essential oil mouthwash to a five-component mixture (thymol, menthol, eucalyptol, and methyl salicylate dissolved in 27% ethanol). They studied the antimicrobial activities of individual Listerine® components and their mixtures. They tested activity against the bacterial strains
Streptococcus mutans, Enterococcus faecalis, and Eikenella corrodens and the yeast
Candida albicans. The established minimum inhibitory concentration (MIC) and the minimum bactericidal/fungicidal concentration (MBC/MFC) assays were applied. None of the combinations of two phenols at the concentrations contained in Listerine® were associated with either an additive or synergistic effect. The same degree of activity was observed against the yeast with thymol as with Listerine. A combination of three of the phenols also exhibited the same activity against the bacteria as Listerine. Similar studies have been performed by other authors [
7,
8,
9,
10].
Essien et al. [
11] studied the antimicrobial activity of volatile constituents from fresh fruits of
Alchornea cordifolia and
Canthium subcordatum. A. cordifolia oil contained 25.3% methyl salicylate
, whereas the oil from
Canthium subcordatum contained only 4.5%. A potent in vitro antibacterial activity against
Staphylococcus aureus (MIC = 78 μg/mL) and marginal antifungal activity against
Aspergillus niger (MIC = 156 μg/mL) were observed for the essential oil from
A. cordifolia. Antibacterial activity against
Bacillus cereus and S. aureus (MIC = 156 μg/mL) and notable antifungal activity against
A. niger (MIC = 39 μg/mL) were observed for the essential oil from
C. subcordatum. However, no appreciable cytotoxic effects on human breast carcinoma cells (Hs 578T) and human prostate carcinoma cells (PC-3) were observed for either essential oil.
Esters are produced by a large number of processes. such as heating carboxylic acids with alcohol in the presence of an acid catalyst. In the Fischer or Fischer-Speier Esterification, the Lewis or Brønstedt acid (
p-TsOH, H
2SO
4) catalyzed esterification of carboxylic acids with alcohols to give esters is a typical reaction in which the products and reactants are in equilibrium [
12]. The equilibrium may be influenced by either removing one product from the reaction mixture (for example, removal of the water by azeotropic distillation or absorption by molecular sieves) or by employing an excess of one reactant.
Alternative reactions employ coupling reagents such as N,N′-dicyclohexylcarbodiimide (DCC or DCCD), in the Steglich Esterification, preformed esters (transesterification), carboxylic acid chlorides or anhydrides [
13]. These reactions avoid the production of water. Another pathway for the production of esters is the formation of a carboxylate anion, which then reacts as a nucleophile with an electrophile. Esters may also be produced by oxidations, namely by the Baeyer-Villiger oxidation and oxidative esterifications.
Many other examples of ester synthesis can be mentioned [
14,
15,
16,
17,
18,
19,
20,
21,
22,
23]. Barbosa et al. [
24] demonstrated that NbCl
5 and Al
2O
3 catalyzed the esterification and etherification of alcohols under microwave radiation. Gryglewicz [
25] also demonstrated that alkaline earth metal compounds act as catalysts for the alcoholysis of oils in the production of esters. Liu et al. [
26] observed that red mud, which is an alkaline residue containing various metal oxides. is effective for the production of biodiesel from oils.
C. Mazzocchia et al. [
27] obtained fatty acid methyl esters from triglycerides using heterogeneous catalysis under microwave radiation. However, among all these examples, very little has been reported regarding the use of NbCl
5 for promoting the esterification or transesterification reactions.
The aim of the present research work was to use pure methyl salicylate (MS) synthesized in this laboratory for the evaluation of the cytotoxic potential in metastatic melanoma cells, a bacterial culture of S. aureus, and in non-tumoral cells of fibroblasts.