ω-Pyridiniumalkylethers of steroidal phenols: new compounds with potent antibacterial and antiproliferative activities

• Published in: Bioorganic & medicinal chemistry 2004-06, Vol.12 (12), p.3357-3362
• Main Authors: Lange, C, Holzhey, N, Schönecker, B, Beckert, R, Möllmann, U, Dahse, H.-M
• Format: Article
• Language: English
• Subjects: Antimicrobial activity; Hybrid molecules; Pyridiniumalkyl salts; Steroids
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.03.046

Antibacterial and antiproliferative activity in dependence on the alkyl chain length. Novel ω-pyridiniumalkylethers of two steroidal phenols were synthesized as compounds with potential antimicrobial activity. 3-Hydroxy-estra-1,3,5(10)-triene-17-one and 1-hydroxy-4-methyl-estra-1,3,5(10)-triene-17-one were reacted with ω,ω′-dibromoalkanes to ω-bromoalkoxy-estra-1,3,5(10)-trienes followed by reaction with pyridine to obtain the desired steroidal ω-pyridiniumalkoxy compounds as bromides. Their antimicrobial activity against strains of multiresistant Staphylococcus aureus (MRSA), a vancomycin resistant Enterococcus faecalis and fast growing mycobacteria depends clearly on the length of the alkyl chain. A strong broadband activity has been found for the compounds with eight or 10 C-atoms; in some cases better than ciprofloxacin or cetylpyridinium salts. In addition, the antiproliferative and cytotoxic activity depends on the chain length, too. The differentiation between antibacterial and cytotoxic activity is better for the steroid hybrid molecules than the cetylpyridinium salts. These new compounds can serve as lead compounds for further optimization.