Antimicrobial and Cytotoxic Activities of Neolignans from Magnolia officinalis

• Published in: Chemistry & biodiversity 2004-03, Vol.1 (3), p.530-537
• Main Authors: Syu, Wan-Jr, Shen, Chien-Chang, Lu, Jang-Jih, Lee, Gum-Hee, Sun, Chang-Ming
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - isolation & purification; Anti-Infective Agents - toxicity; Cell Line, Tumor; Cytotoxins - isolation & purification; Cytotoxins - toxicity; HeLa Cells; Humans; Lignans - isolation & purification; Lignans - toxicity; Magnolia - chemistry; Magnolia - toxicity; Magnolia officinalis; Microbial Sensitivity Tests; Plant Extracts - isolation & purification; Plant Extracts - toxicity; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development; Vancomycin Resistance - drug effects
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.200490046

In the light of the steady increase of infections related to vancomycin‐resistant enterococci (VRE) and methicillin‐resistant Staphylococcus aureus (MRSA), the medicinal plant Magnolia officinalis was subjected to bioassay‐directed fractionation, which led to the isolation of the known neolignans piperitylmagnolol (1), magnolol (2), and honokiol (3) from the MeOH extract. In broth‐microdilution assays, 1–3 exhibited antibacterial activities against VRE and MRSA at minimum‐inhibitory concentrations (MIC) in the range of 6.25–25 μg/ml, compound 1 being the most‐potent antibiotic. The ratio of MBC/MIC (MBC=minimum bactericidal concentration) was ≤2 for all compounds. The kinetics of the antibacterial action of 1 and 3 were studied by means of time‐kill assays; both compounds were bactericidal against VRE and MRSA, their actions being time dependent, or both time and concentration dependent. Magnolol (2) was acetylated to magnolol monoacetate (4) and magnolol diacetate (5) (partial or full masking of the phenolic OH functions). The cytotoxic properties of 1–5 against human OVCAR‐3 (ovarian adenocarcinoma), HepG2 (hepatocellular carcinoma), and HeLa (cervical epitheloid carcinoma) cell lines were evaluated. The CD50 values for compounds 1–3 were in the range of 3.3–13.3 μg/ml, derivatives 4 and 5 being much less potent. This study indicates that piperitylmagnolol (=3‐[(1S,6S)‐6‐isopropyl‐3‐methylcyclohex‐2‐enyl]‐5,5′‐di(prop‐2‐enyl)[1,1′‐biphenyl]‐2,2′‐diol; 1) possesses both significant anti‐VRE activity and moderate cytotoxicity against the above cancer cell lines.