In vitro growth inhibitory effects of cytochalasins and derivatives in cancer cells

The in vitro anticancer activity of eight natural cytochalasins and three hemisynthetic derivatives of cytochalasin B on six cancer cell lines was evaluated. The IC(50) in vitro growth inhibitory concentrations, as determined by an MTT colorimetric assay, ranged between 3 and 90 mu M and did not relate to the intrinsic sensitivity of the cancer cell lines to proapoptotic stimuli. Structure activity relationship (SAR) analyses revealed that the presence of an unmodified hydroxyl group at C-7 of the perhydroisoinsolyl-1-one residue as well as the functionalities and the conformational freedom of the macrocycle are all important features for cytochalasin-mediated anticancer activities in vitro. Computer-assisted phase-contrast microscopy revealed two groups of cytochalasins, i.e., cytotoxic versus cytostatic ones. Our data open new possibilities for tuning cytochalasin targets and developing nontoxic, cytostatic cytochalasins to combat cancers associated with poor prognoses, such as those that display intrinsic resistance to proapoptotic stimuli

In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii.

The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro

Sequestered fulvinol-related polyacetylenes in Peltodoris atromaculata

The Mediterranean dorid nudibranch Peltodoris atromaculata that had been collected while feeding on Haliclona fulva was shown to sequester long-chain fulvinol-like polyacetylene metabolites (compounds 2-5) from the prey. They were isolated along with previously reported bromorenierins from the diethyl ether extracts of both the mollusk and the sponge. Their structures were elucidated by NMR spectroscopy and tandem FABMS analysis. Compound 5 exhibited in vitro growth inhibitory effects against the SKMEL-28 melanoma cell line. © 2014 The American Chemical Society and American Society of Pharmacognosy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Extending the record of bis-γ-pyrone polypropionates from marine pulmonate mollusks.

The isolation and structure elucidation of 10 unreported polypropionate metabolites (compounds 6-15), structurally related to either ilikonapyrone (1) or onchidione (3), from two onchidiid pulmonate mollusk species are discussed. Structure elucidation was achieved by NMR spectroscopy and chemical correlation with model compounds. Evaluation of in vitro growth-inhibitory properties in human cancer cells was also carried out on some of the isolated polypropionates including previously reported onchidione metabolites.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe