Germacrane Sesquiterpene Dilactones from Mikania micrantha and Their Antibacterial and Cytotoxic Activity

Four new germacrane sesquiterpene dilactones, 2 beta-hydroxyl-11 beta,13-dihydrodeoxymikanolide (1), 3 beta-hydroxyl-11 beta,13-dihydrodeoxymikanolide (2), 1 alpha,3 beta-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11 beta,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 mu g/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 mu g/mL, which was close to reference compound vancomycin (MIC 3.125 mu g/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 mu M. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.

Automated summary

Four new germacrane sesquiterpene dilactones, together with five known ones, were isolated from Mikania micrantha. Compound 4 is the first nitrogen-containing sesquiterpenoid isolated from this plant. These compounds showed strong antibacterial activity against various bacteria and cytotoxic activity against tumor cell lines.