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

Four new germacrane sesquiterpene dilactones, 2ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (1), 3ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (2), 1α,3ß-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11ß,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 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/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 µM. 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.

Anti-MRSA Sesquiterpenes from the Semi-Mangrove Plant Myoporum bontioides A. Gray.

The striking rise of methicillin-resistant Staphylococcus aureus (MRSA) infections has become a serious threat to public health worldwide. In an effort to search for new anti-MRSA agents from natural products, a bioassay-guided phytochemical study was conducted on the semi-mangrove plant Myoporum bontioides A. Gray, which led to the isolation of two new sesquiterpene alkaloids (1 and 2) and six known furanosesquiterpenes (3⁻8). Their structures were elucidated on the basis of extensive analysis of their 1D, 2D NMR and mass spectroscopic data. These two new alkaloids (1 and 2) displayed potent anti-MRSA activity with MIC value of 6.25 µg/mL. This is the first report of sesquiterpene alkaloids from the plants of Myoporum genus and their anti-MRSA activity.

Thymol derivatives with antibacterial and cytotoxic activity from the aerial parts of Ageratina adenophora.

Three new thymol derivatives, 7-formyl-9-isobutyryloxy-8-hydroxythymol (1), 7,9-di-isobutyryloxy-8,10-dehydrothymol (2) and 2α-methoxyl-3ß-methyl-6-methylol-2,3-dihydrobenzofuran (3), along with five known ones (4-8), were isolated from the aerial parts of the invasive plant Ageratina adenophora. Their structures were elucidated by extensive spectroscopic analysis and they were all isolated from the aerial part of A. adenophora for the first time. These compounds, except 8, selectively showed in vitro antimicrobial activity against three Gram-(+) and two Gram-(-) bacterial strains. In particular, compounds 1 and 5 showed notable in vitro antimicrobial activity against all five bacterial strains with IC50 values ranging from 3.9 to 15.6 µg mL-1, as compared to reference compound kanamycin sulfate with a MIC value 1.9-3.9 µg mL-1. Compounds 1 and 5 were further revealed to show in vitro cytotoxic activity against three tested human tumor (MCF-7, NCI-H460 and HeLa) cell lines, with IC50 values ranging from 7.45 to 28.63 µM. Compounds 7 and 8 selectively showed slight but detectable in vitro cytotoxicity toward MCF-7 and NCI-H460 cell lines, with IC50 values 44.65-83.19 µM. No cytotoxic effects were detected in the bioassay of the other four thymol derivatives. The present results provide new data to support that the aerial parts of A. adenophora are a rich source of bioactive chemicals valuable in medicinal applications.

Triterpenoids with α-glucosidase inhibitory activity and cytotoxic activity from the leaves of Akebia trifoliata.

Ten pentacyclic triterpenoids including a new multiflorane triterpene acid, 2α,3ß,23-trihydroxymultiflor-7-en-28-oic acid (1), and a new lupane triterpene monoglucoside named akebiaoside C (2), were obtained from the leaves of Akebia trifoliata. Their structures were elucidated by extensive spectroscopic analysis, and they were all isolated from the leaves of A. trifoliata for the first time. These compounds, except 4 and 5, showed in vitro α-glucosidase inhibitory activity much stronger than acarbose. Especially, 2, 3, 6, 8 and 10 displayed in vitro α-glucosidase inhibitory activity with IC50 values from 0.004 to 0.081 mM, which were close or even more potent than corosolic acid (IC50 0.06 mM). Triterpenoids 1, 8 and 10 were further revealed to show moderate in vitro cytotoxic activity against human tumor A549, HeLa and HepG2 cell lines, with IC50 values ranging from 26.5 to 51.9 µM. Compound 9 selectively showed in vitro cytotoxicity toward HeLa and HepG2 cell lines, with IC50 values of 81.49 and 73.47 µM, respectively. These findings provided new data to support that the leaves of A. trifoliata are a rich source in bioactive triterpenoids highly valuable to be developed for medicinal usage.