Lindenane sesquiterpenoid dimers from Chloranthus japonicus inhibit HIV-1 and HCV replication.

Phytochemical investigation on the whole plant of Chloranthus japonicus (Chloranthaceae) led to the isolation and identification of three new lindenane-type sesquiterpenoid dimers, chlorajaponilides F-H (1-3), along with seven known ones (4-10). Their chemical structures were established by extensive spectral evidence. Compounds 1 and 2 are both dimeric sesquiterpenoids featuring a rare hydroperoxy group at C-5. All compounds were tested for their activities on wild type HIV-1 replication and compounds 1, 2, 5, and 9 were effective with EC50 values from 3.08 to 17.16µM. All these four compounds showed the same inhibitory effects on the two NNRTI-resistant HIV strains as on wild-type HIV-1 with EC50 change folds from 0.61 to 1.6µM. Furthermore, compounds 1, 5, and 9 exhibited inhibitory activities on HCV replication with the similar potency as their activities on HIV-1. Our finding may provide a clue to address the problem of HIV-1 and HCV co-infection.

Plantagiolides K-N, three new withanolides and one withanolide glucoside from Tacca plantaginea.

Phytochemical investigation of the whole plants of Tacca plantaginea led to the isolation of 3 new withanolides and one new withanolide glucoside, named plantagiolides K-N (1-4), together with one known withanolide, 4 known withanolide glucosides, and 2 known taccalonolides. Their structures were elucidated by extensive spectroscopic analysis. Compound 4 is the first withanolide glycoside which the sugar moiety is attached at C-7. The effects of the some of isolates on TNFα-induced NF-κB transcriptional activity and cytotoxicity were evaluated.

Three steroids with unique structural feature of 5ß-Spirostan-1ß,3ß,17α-trihydroxyl from Reineckia carnea.

A new spirostanol sapogenin and two spirostanol saponins, tentatively named reineckiagenin A (1), reineckiagenoside A (2), and reineckiagenoside B (3), were isolated from the whole plant of Reineckia carnea. By detailed analysis of their 1D and 2D NMR spectra, chemical methods, and by comparison with spectra data of known compounds, the structures of the new steroids were determined to be 25(S)-5ß-spirostan-1ß,3ß,17α-triol (1), 25(S)-5ß-spirostan-1ß,3ß,17α-triol 1-O-ß-D-xylopyranoside (2), 25(S)-5ß-spirostan-1ß,3ß,17α-triol 1-O-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranoside (3). Compounds 1, 2, and 3 are the first naturally occurring steroids with unique structural feature of 5ß-spirostan-1ß,3ß,17α-trihydroxyl.

HL-37, a novel anthracene derivative, induces Ca(2+)-mediated apoptosis in human breast cancer cells.

HL-37, a novel anthracene derivative, exhibited potent anticancer activity in many kinds of cancer cells. However, the exact mechanism and signaling pathway involved in HL-37-induced apoptosis have not been fully elucidated. Therefore, we explored the mechanisms of HL-37-mediated apoptosis in MCF-7 and MDA-MB-435 human breast cancer cells. When MCF-7 cells or MDA-MB-435 cells were co-incubated with HL-37, the percentage of apoptotic cell and S phase of cell cycle was markedly increased. In addition, a rise in intracellular calcium levels, ROS production, phosphorylation of JNK and activation of calpain were found in both MCF-7 cells and MDA-MB-435 cells after exposure to HL-37. With the HL-37-mediated reduction of mitochondrial membrane potential, cytochrome c was released from mitochondria to cytosol. Moreover, HL-37 strongly induced cleavage of caspase-4, caspase-9, as well as caspase-3 in MDA-MB-435 cells, whereas, activation of caspase-4, caspase-9 and caspase-7 but not caspase-3 was detected in MCF-7 cells. These results suggested that HL-37 induced MDA-MB-435 and MCF-7 cells apoptosis via oxidative stress and Ca(2+)/calpain/caspase-4 pathway.

Anti-tumour effects of HL-37, a novel anthracene derivative, in-vivo and in-vitro.

Many anthracene derivatives possess excellent anti-tumour activity and are extensively used clinically as anti-tumour agents. However, their clinical use is frequently limited by emergence of multidrug resistance (MDR) in tumour cells. Therefore, new agents with the ability to overcome MDR are needed for cancer treatment. HL-37, a novel anthracene derivative, exhibited potent anti-cancer activity in both drug-sensitive (K562) and multidrug-resistant (K562/DOX) leukaemia cells. Mechanistically, we found that HL-37 was neither a substrate nor an inhibitor of P-glycoprotein (P-gp) and could overcome apoptotic resistance via up-regulation of p53 protein and down-regulation of Bcl-xL protein. In addition, HL-37 also induced K562/DOX cell apoptosis and a decrease in G(0)/G(1) phase. Moreover, reduction of mitochondrial membrane potential, release of cytochrome c and an increased expression of cleaved protein fragment of caspase-3, caspase-9 and caspase-8 were also observed. Importantly, HL-37 was found to be better tolerated and more effective at inhibiting tumour growth than bisantrene in a xenograft mouse model.

Octanorcucurbitane and cucurbitane triterpenoids from the tubers of Hemsleya endecaphylla with HIV-1 inhibitory activity.

Two new cucurbitacins, endecaphyllacins A (1) and B (2), together with six known analogues (3-8), were isolated from the tubers of Hemsleya endecaphylla. The structures of 1 and 2 were elucidated by NMR and MS spectroscopic analysis. The relative stereochemistry of 1 was determined by single-crystal X-ray diffraction. Compound 4 (cucurbitacin B) showed potent anti-HIV-1 in C8166 cells (EC=0.09 microg/mL) with a selectivity index of 16.7.

[Synthesis and antibacterial activity of 2-(3-pyridyl)-5-([(5-aryl-1,3,4-oxadiazol-2-yl) methylene]thio)-1,3,4-oxadiazoles].

AIM: Studies on synthesis and antibacterial activity of new heterocycles. METHODS: The cyclocondensation of [(3-pyridyl)-1,3,4-oxadiazol-2-yl] thio acetic acid with various aroyl hydrazines in the presence of POCl3 and xylene gave the corresponding titled compounds, and the in vitro antibacterial activity was primarily evaluated by the method of cupplate diffusion solution. RESULTS: Sixteen novel titled compounds were synthesized, their structures were confirmed by IR, 1HNMR, MS and elemental analysis. Biological screening results demonstrated that most of the compounds prepared displayed potential antibacterial activity. CONCLUSION: Oxadiazoles incorporting pyridyl oxadiazole ring may be usefully antibacterial candidate drugs.