The syntheses of two platinum(ii) dithiocarbamate complexes (1 and 2) that show quinoplatin- and phenanthriplatin-type axial protection of the Pt-plane are described. The Pt-plane of complex 2 is axially more protected than that of complex 1. Furthermore, both complexes adopt two different stereochemical conformations in the solid state (based on single-crystal X-ray structures) owing to the structurally flexible piperazine backbone; i.e., C-e,e-Anti (1) and C-e,a-Syn (2), where "C" stands for the chair configuration, "e" and "a" stand for the equatorial and axial positions and "Anti" (opposite side) and "Syn" (same side) represent the relative orientations in space of the terminal substituents on the piperazine ring. In complex 2, the C-e,a-Syn conformation may provide additional steric hindrance to the Pt-plane. Despite the lower lipophilicity of 2 as compared to that of 1, the in vitro anticancer action against selected cancer cell lines is better for the former revealing the superior role of the axial protection over lipophilicity in modulating anticancer activity. The activity against the cancer promoting protein NF-κB signifies that the mode of cancer cell death may be the result of hindering the activity of NF-κB in the initiation of apoptosis. The apoptotic mode of cell death has been established earlier in a study using Annexin V-FITC. Finally, DNA binding studies revealed that the complex-DNA adduct formation is spontaneous and the mode of interaction is non-intercalative (electrostatic/covalent).
Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, as an anti-pyretic and as an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by its inhibition of iNOS (inducible nitric oxide synthase) and the release of PGE2, IL-6, and IL-8. We also measured its anti-allergic effect by its inhibition of beta-hexosamidase release. An HPLC experiment after extraction with 95% EtOH at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressor. The content of lycorine varied, depending on the type of plant tissue analyzed and the extraction method. In an anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells, the ethanol extract of Crinum asiaticum showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 58.5 microg/ml). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show any cytotoxicity, but did show a cell proliferation effect against LPS (a 10 approximately 60% increase in cell viability). In an assay to determine inhibition of the H2O2-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentration (>0.0025%). In order to investigate the skin-sensitizing potentials of the extract of Crinum asiaticum, a human clinical test was performed after repeated epicutaneous 48-h applications under an occlusive patch (RIPT). The repeated and single cutaneous applications of Crinum asiaticum Linne var. japonicum extract under the occlusive patch did not provoke any cumulative irritation and sensitization reactions. The result showed that the extract of Crinum asiaticum Linne var. japonicum has a sufficient anti-inflammatory effect. Therefore, Crinum asiaticum Linne var. japonicum extract may be useful for development as an ingredient in cosmetic products.