Jeehee Suh

Cardioselective anti-ischemic ATP-sensitive potassium channel (KATP) openers: Benzopyranyl indoline and indole analogues

This paper describes the design, syntheses, and biological evaluations of novel ATP-sensitive potassium channel (K(ATP)) openers, benzopyranyl indoline and indole derivatives. Among those, two enantiomers of indoline-2-carboxylic ethyl esters (14, 18) showed the best cardioprotective activities both in vitro and in vivo, while their vasorelaxation potencies were very low (concentration for 50% inhibition of vasorelaxation >30 microM). The cardioprotective effect of 14 was completely reversed by 5-hydroxydecanoate, a selective mitochondrial K(ATP) blocker, indicating its provable protective mechanism through the mitochondrial K(ATP) opening. In addition, we performed conformational analyses using 2D-NMR, X-ray crystallography and molecular modeling to study the structure-activity relationships in this series of compounds.

Synthesis and Biological Evaluation of N‐aryl‐4‐aryl‐1,3‐Thiazole‐2‐Amine Derivatives as Direct 5‐Lipoxygenase Inhibitors

Biological evaluation of N‐aryl‐4‐aryl‐1,3‐thiazole‐2‐amine derivatives was examined for anti‐inflammatory activity in in vitro and in vivo assays. The thiazole compounds showed direct inhibition of 5‐lipoxygenase (LOX) that is a key enzyme of leukotrienes synthesis and involved in the inflammation‐related diseases, including asthma and rheumatoid arthritis. To optimize biological activity, we synthesized 1,3‐thiazole‐2‐amine derivatives and investigated for structure and activity relationship. Especially, N‐(3,5‐dimethylphenyl)‐4‐(4‐chlorophenyl)‐1,3‐thiazole‐2‐amine was shown to have a potent anti‐inflammatory activity as a 5‐LOX inhibitor.

Synthesis and biological evaluation of 3-substituted-benzofuran-2-carboxylic esters as a novel class of ischemic cell death inhibitors

A series of 3-substituted-benzofuran-2-carboxylic esters was synthesized and evaluated for biological activity as ischemic cell death inhibitors in H9c2 cells and rat primary cardiac myocytes under conditions of oxygen and glucose deprivation. The introduction of a sulfur atom at the three-position substituent of the benzofuran ring markedly improved ischemic cell death inhibitory potency. In particular, 3-[2-(4-nitro-phenylsulfanyl)-acetylamino]-benzofuran-2-carboxylic acid ester (10) (EC(50)=0.532 μM, cell death=6.18%) and 4-chloro-3-[3-(pyridin-2-ylsulfanyl)-propionylamino]-benzofuran-2-carboxylic ester (18) (EC(50)=0.557 μM, cell death=7.02%) were shown to be the most potent in this series of benzofuran analogs.

1098 Expression of several biologic markers as prognostic factors in patients with non-small cell lung cancers

Despite modem diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. With better understanding of tumor biology, one may improve survival through proper treatment. Here we present the clinical significance of several biologic markers as prognostic markers in patients with non-small cell lung cancers. The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidennal growth factor receptor (EGFR), p53 and/or blood group antigen A (BGAA) using immunohistochemistry in 46 cases patients with non-small cell lung cancers. The results were as follows: (1) The expression of BGAA was correlate with better survival in median survival and in 2-year survival and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. (2) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. (3) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. In conclusion, it is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor and also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.