Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid.

A series of novel thiourea α-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.

Synthesis and antitumor activities of novel α-aminophosphonates dehydroabietic acid derivatives.

A series of novel α-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage.

Jacaranone analogs from Senecio scandens.

Bioassay-guided fractionation of the ethanolic extract of Senecio scandens led to the isolation of four new compounds 4, 5, 7, and 8, along with four known jacaranone analogs (1, 2, 3, 6). Their structures were elucidated on the basis of spectral and chemical evidence. Compound 7 was obtained as a tautomeric mixture of alpha/beta-epimer. The cytotoxic activities of these compounds were evaluated. Among these, compounds 5 and 8 showed potent cytotoxicities. The benzoquinone derivative, jacaranone ethyl ester (1), was the major cytotoxic constituent in this plant with IC(50)s at a range of 0.5-1.0 microg/ml against various tumor cell lines. The SAR of these jacaranone analogs (1-8), isolated from S. scandens, was also discussed.

On the chemical constituents of Dipsacus asper.

Bioassay-guided fractionation of 95% EtOH extract from the roots of Dipsacus asper lead to the isolation of some phenolic acids (caffeic acid, 2,6-dihydroxycinnamic acid, vanillic acid, 2'-O-caffeoyl-D-glucopyranoside ester, and caffeoylquinic acid) as the major active components, and five new iridoid glucoside dimers (1-5) and one new iridoid glucoside monomer (6), other known iridoid glycosides loganin, cantleyoside, triplostoside A, lisianthioside, 6'-O-beta-D-apiofuranosyl sweroside, as well as triterpenoids oleanic acid and akebiasaponin D. The structures of new compounds 1-6 were determined as dipsanosides C (1), D (2), E (3), F (4), G (5), and 3'-O-beta-D-glucopyranosyl sweroside (6) by spectroscopic, including 1D and 2D NMR techniques, and chemical methods.

Jacaranone glycosides from Senecio scandens.

Bioassay-guided fractionation of the ethanol extract of Senecio scandens led to the isolation of four new compounds 1-4. These compounds were obtained as tautomeric mixture of alpha/beta epimers, but their structures were confirmed unambiguously by 1D and 2D NMR spectra and LC NMR technology. 1H NMR spectra of pure 1alpha and 1beta were furnished by HPLC NMR technology. Compounds 1-4 exhibited moderate cytotoxicities against five tumor cell lines.

Two novel tetrairidoid glucosides from Dipsacus asper.

[reaction: see text] Two new iridoid glucoside tetramers, dipsanosides A (1) and B (2), the first-reported iridoid tetramers with four glucosides, were isolated from Dipsacus asper. Their structures were determined by analysis of 1D and 2D NMR data as well as by comparison with model compounds. Their cytotoxicities were tested, but neither of them showed obvious activity.