Rumiko Shimazawa

Thalidomide and its analogues as cyclooxygenase inhibitors

Thalidomide showed cyclooxygenase (COX)-1/2 inhibitory activity with a potency comparable to that of aspirin. Structural development studies of thalidomide resulted in potent COX-1/2 inhibitors, and COX-1-selective and COX-2-selective inhibitors.

Novel small molecule nonpeptide aminopeptidase n inhibitors with a cyclic imide skeleton.

A novel series of small molecule nonpeptide aminopeptidase N (APN) inhibitors with a N-phenylphthalimide or N-phenylhomophthalimide skeleton were prepared. Evaluation of their protease inhibitory activities revealed that (i) some N-phenylphthalimide analogs are potent APN inhibitors, but they are also inhibitors of another protease, dipeptidylpeptidase IV (DPP-IV), and (ii) some N-phenylhomophthalimide analogs, including 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22), are potent and specific inhibitors of APN without DPP-IV-inhibitory activity. The structure-activity relationship studies of N-phenylphthalimides and N-phenylhomophthalimides are reviewed. PIQ-22 showed potent tumor-cell invasion-inhibitory activity.

Nonpeptide small-molecular inhibitors of dipeptidyl peptidase IV: N-phenylphthalimide analogs

A novel series of nonpeptide small-molecular dipeptidyl peptidase IV (DPP-IV) inhibitors with an N-phenylphthalimide skeleton has been developed. Some of the compounds, including 4-amino-(2,6-dimethylphenyl)phthalimides (7), 4- and 5-hydroxy-(2,6-diethylphenyl)phthalimide (11 and 14), 4-hydroxy-(2,6-diisopropylphenyl)phthalimide (12), and thiocarbonyl analogs of (2,6-diisopropylphenyl)phthalimide and their 4,5,6,7-tetrafluorinated derivative (18, 19 and 20), were more potent than the well-known DPP-IV-specific inhibitor, Pro-boroPro (PBP). Among them, 18 was revealed to be a DPP-IV-specific inhibitor, while the others also showed inhibitory activity toward another peptidase, aminopeptidase N (APN).

Fluorescent and photoaffinity labeling probes for retinoic acid receptors

A fluorescent probe for retinoid receptors (RARs) was designed and prepared. The probe consists of a retinoid moiety and a dansyl moiety, i.e., 2-[3-(5-dimethylaminonaphthalene-1-sulfonyl)- aminopropyl-1-oxy]-4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carboxamido]benzoic acid: DAM-3. DAM-3 specifically bound RARs. Additionally, a photoreactive RAR fluorescent probe was designed and prepared, i.e., 2-[3-(5-azidonaphthalene- 1-sulfonyl)aminopropyl-1-oxy]-4-[(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (ADAM-3). ADAM-3 irreversibly and specifically bound RARs using ultraviolet irradiation.

Water-soluble Zimmerman's molecular tweezer analogs: Dextran-coupling method for solubilization

Abstract Water-insoluble Zimmermans molecular tweezers were converted to water-soluble species by coupling with dextran polymer. The dextran-coupled molecular tweezers showed high affinity for adenine derivatives in an aqueous buffer, with the major mode of interaction being considered to be hydrophobic interaction.

DNA-binding ability of non-diynene class of dynemicins and Aza-anthraquinones

Abstract DNA-binding ability of five non-diynene dynemicins and four related synthetic aza -anthraquinones ( 1–4 ) was studied by measurements of UV absorption shifts and electrophoretic behavior of the complexes with DNA.