A New 1,2-Naphthoquinone Derivative with Anti-lung Cancer Activity.

1,2-Naphthoquinone (2-NQ) is a nucleophile acceptor that non-selectively makes covalent bonds with cysteine residues in various cellular proteins, and is also found in diesel exhaust, an air pollutant. This molecule has rarely been considered as a pharmacophore of bioactive compounds, in contrast to 1,4-naphthoquinone. We herein designed and synthesized a compound named N-(7,8-dioxo-7,8-dihydronaphthalen-1-yl)-2-methoxybenzamide (MBNQ), in which 2-NQ was hybridized with the nuclear factor-κB (NF-κB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) as a nucleophile acceptor.

Development of chimeric receptor activator of nuclear factor-kappa B with glutathione S-transferase in the extracellular domain: Artificial switch in a membrane receptor.

Various chimeric receptors have been developed and used for biological experiments. In the present study, we constructed three types of chimeric receptor activator of nuclear factor-kappa B (RANK) with the glutathione S-transferase (GST) protein in the extracellular domain, and stimulated them using newly synthesized chemical trimerizers with three glutathiones. Although this stimulation did not activate these proteins, we unexpectedly found that the chimera named RANK-GST-SC, in which GST replaced a major part of the RANK extracellular domain, activated nuclear factor-kappa B (NF-κB) signaling approximately sixfold more strongly than wild-type RANK without the ligand.

Interruption of Vif/Elongin C interaction: In silico and experimental elucidation of the underlying molecular mechanism of benzimidazole-based APOBEC3G stabilizers.

In 2014, two novel and promising benzimidazole-based APOBEC3G stabilizers MM-1 and MM-2 (MMs) were uncovered with an elusive mechanism of action. Vif-APOBEC3G axis has been recognized as a novel therapeutic target for anti HIV-1 drug development. The unexplored mechanism of MMs hindered their further development into lead compounds.

HSP70 induction by bleomycin metal core analogs.

Induction of heat shock protein 70 (HSP70) is known to be effective against various diseases. We are interested in HSP70 induction capability of an antitumor antibiotic bleomycin which produces oxidative stress by iron chelate formation and oxygen activation in a cell. The HSP70 induction activity of bleomycin and its six metal core analogs was examined, and a compound HPH-1Trt of 10 μM was found to induce this protein in a pheochromocytoma cell line and some T cell and monocytic cell lines.

Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system.

Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251.

l-Histidyl-glycyl-glycyl-l-histidine. Amino-acid structuring of the bleomycin-type pentadentate metal-binding environment capable of efficient double-strand cleavage of plasmid DNA.

A tetrapeptide, l-histidyl-glycyl-glycyl-l-histidine (HGGH), was synthesized and the pUC19 plasmid DNA cleaving activity by copper(II) complex of HGGH (Cu(II)-HGGH) was investigated. Cu(II)-HGGH showed bleomycin-like DNA cleaving activity and, at 50nM, converted a supercoiled DNA efficiently to a linear DNA in the presence of 500μM H2O2/sodium ascorbate through an oxidative pathway.