Zhi-Xin Liao

Synthesis and antitumor activities of novel α-aminophosphonate derivatives containing an alizarin moiety.

A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca(2+) and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.

Combretastatin A-4 Analogue: A Dual-Targeting and Tubulin Inhibitor Containing Antitumor Pt(IV) Moiety with a Unique Mode of Action.

Three new Pt(IV) complexes comprising a combretastatin A-4 analogue were designed and synthesized. The resulting antitumor Pt(IV) complexes could significantly improve the antiproliferative activity and overcome the drug resistance of cisplatin in vitro. Interestingly, these novel compounds not only can carry the DNA binding Pt(II) warhead into the cancer cells but also have a small molecule fragment that can inhibit tubulin polymerization. Among them, complex 13, which was attached to an inhibitor of tubulin at one axial position of Pt(IV) octahedral coordination sphere, could effectively enter cancer cells, arrest the cell cycle in HepG-2 cancer cells at G2/M phases, and induce activation of caspases triggering apoptotic signaling via the mitochondrial-dependent apoptosis pathways. Moreover, complex 13 has the ability to effectively inhibit the tumor growth in the HepG-2 xenograft model without causing significant loss of animal body weight in comparison with cisplatin.

A new pregnane glycoside from Rubus phoenicolasius and its antiproliferative activity

Chemical investigations of the whole plant ethanol extract of Rubus phoenicolasius led to the isolation and identification of a new pregnane glycoside, 3-O-β-glucopyranosyl-3β,15β-dihydroxypregn-5-en-20-one (1), along with other nine known compounds (2–10). All the isolates were reported from this plant for the first time. The structure of compound 1 was determined by detailed analysis of its spectral data including 1D and 2D NMR. In vitro anti-proliferative activities of compounds 1–3 on MCF-7 and NCI-H460 tumour cell lines were evaluated, and compound 1 was active against the two cell lines with IC50 values of 15.6 and 13.5 μM, respectively.

Eremophilane Sesquiterpenes from the Genus Ligularia.

Ligularia speices are widely used in Asian folk medicines for the treatment of various human diseases. Eremophilane‐type sesquiterpenes are abundant and typical secondary metabolites found in this genus. Over 500 eremophilanes reported from members of Ligularia are reviewed in this article together with bioactivity data in an effort to highlight the development in this field.

First separation of four aromatic acids and two analogues with similar structures and polarities from Clematis akebioides by high-speed counter-current chromatography

In this paper, we report an efficient method by high-speed counter-current chromatography for the first separation of four aromatic acids and two analogs with similar structures and polarities from Clematis akebioides. First, the ethyl acetate extract was treated by silica gel column chromatography to enrich the target compounds. And then the fraction with target compounds were purified by high-speed counter-counter chromatography using a two-phase solvent system consisting of chloroform/acetonitrile/water (10:6:4, v/v). The results showed high-speed counter-current chromatography could be a powerful technology for the separation of compounds with similar structures and polarities. Besides, it was found acetonitrile could be a good methanol substitute when a chloroform/methanol/water system could not provide a good separation factor. This study provides a reference for the separation of compounds from Clematis akebioides.

A new phenylpropanoid from the roots of Euphorbia nematocypha

A phytochemical investigation of the ethanolic extracts of the dried roots of Euphorbia nematocypha resulted in the isolation of a new phenylpropanoid, 16-O-caffeoyl-16-hydroxylhexadecanoic acid (1), together with 23 known compounds (2–24). Their structures were elucidated on the basis of spectroscopic data. Compound 1 was first to be isolated as a caffeic acyl long chain alkyl acid from the family Euphorbiaceae. The new isolated phenylpropanoid showed potent cytotoxic activities against the MCF-7 and HeLa cell lines.

The glycosides from Lomatogonium rotatum

A new phenyl glycoside, 2-(3′-O-β-D-glucopyranosyl)benzoyloxygentisic acid (1), along with seven known glycosides 2–8 was isolated from Tibetan herbal medicine Lomatogonium rotatum. The structures of the compounds were elucidated by spectroscopic methods including 1D and 2D NMR techniques and MS data.

Platinum(IV) complexes conjugated with phenstatin analogue as inhibitors of microtubule polymerization and reverser of multidrug resistance

Pt(IV) complexes comprising a phenstatin analogue, as dual-targeting Pt(IV) prodrug, were designed and synthesized. They were found not only to carry the DNA binding platinum warhead into the tumor cells, but also to have a small molecular unit to inhibit tubulin polymerization. In vitro evaluation results revealed that Pt(IV) complexes showed better and more potent activity against the test human cancer cells including cisplatin resistant cell lines than their corresponding Pt(II) counterparts. In addition, the Pt(IV) derivative of cisplatin, complex 10, exhibited highly selective inhibition in human cancer cells and displayed no obvious toxicity to two human normal cell lines, respectively. Mechanism study suggested that complex 10 induced cell-cycle arrest at the G2/M phase and caused apoptotic cell death of human lung cancer NCI-H460 cells through the mitochondrial mediated pathway. Moreover, complex 10 effectively inhibited the tumor growth in the NCI-H460 xenograft model.

A trehalose ester from Lancea tibetica

A phytochemical study of the 95% ethanolic extract of the whole plant of Lancea tibetica Hook. f. et Thoms. led to the isolation of a new trehalose ester, 6-O-undecanoyl-α,β-trehalose (1), along with 23 known compounds (2–24), of which compounds 2–17 were isolated from this plant for the first time. The structures of these compounds were established on the basis of spectroscopic methods. Compound 1 was evaluated for their in vitro anti-proliferative activities against MCF-7, NCI-H460 and Hep-G2 tumour cell lines. Compound 1 exhibited potent inhibitory activity against NCI-H460 cell growth, in contrast to moderate cytotoxic activity against MCF-7 and Hep-G2 cells.

Chemical constituents of Caryopteris tangutica

A new compound (1), along with 18 known compounds, was isolated from Caryopteris tangutica. On the basis of spectroscopic methods, with special emphasis on 1D- and 2D-NMR techniques, the structure of the new compound was characterised as 6-hydroxy-6-methylcyclohex-2-en-1-one (1).