The aim of this study was to evaluate the biological activity and pharmacological activity of several amphiphilic liquid-crystalline compounds (LCs), i.e. phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit, to explore novel anti-cancer functions of the LCs. The anti-cancer properties of the LCs were investigated in A549 human lung cancer cells by assessing cell growth, cell cycle distribution, and cell signaling pathways using a flow cytometer and a Western blot analysis. In addition, the effect of LCs on the growth of WI-38 normal fibroblasts was examined. Consequently, the phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through G1 phase arrest in A549 cells. Further analyses using phenylpyrimidine derivatives and precursors of a cyanobiphenyl compound demonstrated the structure-activity relationships. One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts. As a result, a novel pharmacological function was hypothesized to be inherent in the structure of the LCs themselves, and the dependence of the tumor-specific activity on the hydrophobic group of phenylpyrimidine derivatives therefore remains an interesting issue. Our results suggest the possibility that the LCs themselves may act as a novel type of chemotherapeutic agent.

We investigated biological activity of a homologous series of 4-cyano-4′-(ω-hydroxyalkyloxy)biphenyl. The amphiphilic compounds with a nematic phase were found to exhibit marked inhibition of cell proliferation of A549 human lung carcinoma cell lines, although they showed no such inhibition against WI-38 normal fibroblast cell lines under identical conditions.

BackgroundThe aim of this study was to evaluate the biological and pharmaceutical activities of 14 amphiphilic liquid-crystalline compounds (LCs), i.e, phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit.ResultsThe cytotoxic properties of the LCs on the cell growth, cell cycle distribution, and cell signaling pathway of U937 human leukemic monocyte lymphoma cells were assessed by flow cytometry and western blot analysis. Some LCs showed cytostatic effects, suppressing cell growth via S-phase arrest and without apoptosis in U937 cells. To investigate the mechanisms of the LC-induced S-phase arrest, proteins relevant to cell cycle regulation were investigated by western blot analysis. The rate of LC-induced S-phase arrest was congruent with the decreased expression of MCM2, cyclin A, cyclin B, CDK2, phospho-CDK1 and Cdc25C. Observed changes in cell cycle distribution by LC treated might be caused by insufficient preparation for G2/M transition. Considering the structure of the LCs, the rod-like molecules displaying cytotoxicity against U937 cells possessed flexible spacers with no bulky polar group attached via the flexible spacer.ConclusionsOur results revealed that some LCs showed cytotoxic properties against non-solid type tumor human leukemic cells via LC-induced S-phase arrest and decreasing expression of several cell cycle related proteins.

We have designed an amphiphilic compound in which phenylpyrimidine and d-glucamine are connected via a flexible spacer. The compound shows two thermotropic lamellar bilayer mesophases with different layer spacings. The liquid-crystalline compound showed cytostatic activity against A549 human lung carcinoma cell lines, however an amphiphilic phenylpyrimidine derivative, d-glucamine, and an equimolar mixture of them were not active on cell lines under identical conditions.

We investigated the anti-tumor activity and mesogenic properties of 4-cyano-4 0 -(6hydroxyhexyloxy)biphenyl (I-CN), 4-methyloxy-4 0 -(6-hydroxyhexyloxy)biphenyl (I-OMe) and their binary mixtures. The anti-tumor properties of the materials were investigated in A549 human lung cancer cells by assessing cell growth, cell cycle distribution and cell signaling pathways using flow cytometry and Western blot analysis. An equimolar mixture of I-CN (2.5 mM) and I-OMe (2.5 mM) exhibited stronger inhibition of cell proliferation in A549 human lung cancer cells than I-CN or I-OMe. The mixture did not affect cell proliferation against WI-38 normal fibroblasts. Both thermotropic and lyotropic mesogenic properties of the mixture indicate that molecular aggregation between I-CN and I-OMe occurs at a concentration of micromolar order. These results reveal that the supramolecular assembly composed of different molecules plays an important role in the biological activity of liquid-crystalline molecules.