Antibacterial activity of acyl and epoxide derivatives of β-sitosterol and cycloartanes

Nowadays, infectious diseases still remain the second leading cause of death worldwide [1]. The ability that microorganisms have to develop resistance to drugs along with population mobility and globalization have turned the possibility of epidemics/pandemics a really serious health problem. Currently, infectious diseases can not only spread faster, but they also appear to emerge more quickly than before [2]. There is, therefore, an increased need for new and more effective antibacterial chemotherapeutic agents. Plants have long been a source of medicines, and an impressive number of modern drugs have been isolated from plants. According to Cragg [3], from the 109 new antibacterial drugs approved by FDA during 1981–2006, 69% were natural products or natural product derivatives. The aim of this work was to find out new antimicrobial compounds from plant sources through derivatization of?-sitosterol and tetracyclic triterpenes with the cycloartane scaffold, previously isolated from Euphorbia species [4]. Triterpenes and steroids are a good raw material because they are easily obtained from Euphorbia crude extracts and in large amounts. Sixteen monoacylated derivatives at C-3 were prepared by using different carboxylic anhydrides or acyl chlorides. Epoxide derivatives of both original compounds and esters were also prepared. All compounds were tested against reference and multiresistant bacterial strains: Gram-positive (Enteroccocus faecalis, Staphylococcus aureus and Mycobacterium smegmatis); Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Acinetobacter baumannii and Klebsiella pneumoniae) and yeast Candida albicans. The minimum inhibitory concentrations (MIC) were determined by using the serial broth microdilution method. Several derivatives have showed lower MIC values when compared to parent compounds (MIC: 30–73µM) Remarkable enhancement on the antibacterial activity was observed for all benzoyl and para-substituted benzoyl chlorides (MIC: 28–60µM) against Staphylococcus aureus and Mycobacterium smegmatis.

References: 1. Courvalin P (2005) Emerg. Infect. Dis. 11:1503–06.

2. The world health report 2007 (2007) http://www.who.int/whr/2007/en/index.html.

3. Cragg, GM, Newman, DJ. (2001) Pharm. Biol. 39:8–1.

4. Madureira, AM et al. (2003) Nat. Prod. Res. 17:375–80.