• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1024-1028
• /
• 2003

A prolyl endopeptidase inhibitor was isolated from the ethyl acetate soluble fraction of Phyllanthus ussurensis. The active compound was identified as an ellagitannin, corilagin. It was shown to non-competitively inhibit prolyl endopeptidase (PEP) with the $IC_{50}$ value of $1.17 \times $10^{-6}\mu$M. The Ki value was $6.70 \times 10^{-7}$ M. Corilagin was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase, indicating that it was relatively a specific inhibitor of PEP. Corilagin also effectively inhibited reactive oxygen species such as hydroxide and superoxide anion radical, hydrogen peroxide, and DPPH. Especially, corilagin showed potent scavel1ging activity on the superoxide anion radical in the ESR method ($IC_{50} =3.79 \times 10^{-6}$M) as well as xanthine oxidase system.

• Archives of Pharmacal Research
• /
• v.26 no.8
• /
• pp.612-619
• /
• 2003

In this study, we evaluated the effects of oral administration of DA-8159, a selective phosphodiesterase-5 inhibitor, on the development of pulmonary hypertension (PH) induced by monocrotaline (MCT). Rats were administered either MCT (60 mg/kg) or saline. MCT-treated rats were divided into three groups and received orally administered vehicle, or 1 mg/kg or 5 mg/kg of DA-8159, twice a day for twenty-one days. The MCT group demonstrated increased right ventricular weights, medial wall thickening in the pulmonary arteries, myocardial fibrosis and the level of plasma cyclic guanosine monophosphate (cGMP), along with decreased body weight gains. However, DA-8159 markedly and dose-dependently reduced the development of right ventricular hypertrophy and medial wall thickening. DA-8159 also amplified the increase in plasma cGMP level and significantly increased the level of lung cGMP, compared with the MCT group. Although the body weight gain was still lower from the saline-treated control group, DA-8159 demonstrated a significant increase in body weight gains, in both 1 mg/kg and 5 mg/kg groups, when compared with the MCT group. In myocardial morphology, MCT-induced myocardial fibrosis was markedly prevented by DA-8159. These results suggest that DA-8159 may be a useful oral treatment option for PH.

• Biomolecules & Therapeutics
• /
• v.29 no.5
• /
• pp.562-570
• /
• 2021

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1997.04a
• /
• pp.100-100
• /
• 1997

To treat peptic ulcer diseases, many potent proton pump inhibitors have been developed for suppressing the gastric acid secretion in clinical patients. However, most of these agents have common irreversible mechanisms against H$\^$+/, K$\^$+/-ATPase which might be the cause of hypergastrinemia and ECL cell hyperplasia. Therefore, the development of new reversible inhibitors is prompted. In this study, we investigated the inhibitory mechanism of a newly synthesized proton pump inhibitor, YJA20379-8 using lyophilized hog gastric microsomes. YJA20379-8 inhibited K$\^$+/-stimulated H$\^$+/K$\^$+/-ATPase activity uncompetitively with respect to K$\^$+/, and in the other hand, showed competitive inhibitory pattern with ATP, respectively. From these data, we suggest that YJA20379-8 may be a proton pump inhibitor with a new inhibitory mechanism.

• Bulletin of the Korean Chemical Society
• /
• v.27 no.7
• /
• pp.1075-1078
• /
• 2006

• Bulletin of the Korean Chemical Society
• /
• v.34 no.7
• /
• pp.2199-2202
• /
• 2013

• Bulletin of the Korean Chemical Society
• /
• v.23 no.11
• /
• pp.1545-1547
• /
• 2002

A new insecticide, bistrifluron acts as an inhibitor of insect development and interferes with the cuticle formation of insects. Since it shows low acute oral and dermal toxicities, it can be one of potent insecticides. Based on X-ray crystallography, NMR spectroscopy and molecular modeling, the structural studies of bistrifluron have been carried out.

• International Journal of Industrial Entomology and Biomaterials
• /
• v.15 no.2
• /
• pp.161-164
• /
• 2007

While searching for ${\alpha}$-glucosidase inhibitors, the active compound was found in a methanol extract of Burthus martensi Kirsch. The separation of the active compound was performed using various chromatography methods and the physico-chemical properties of the purified compound were characterized. The compound showed very potent inhibitory activity against ${\alpha}-glucosidase$ with an $IC_{50}$ value of $5.3\;{\mu}g/ml$. Lineweaver-Burk plot indicated that its inhibition of ${\alpha}-glucosidase$ was competitive.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.12
• /
• pp.3885-3887
• /
• 2013

• Archives of Pharmacal Research
• /
• v.12 no.4
• /
• pp.276-281
• /
• 1989

Selective inhibition of seven new PDE inhibitors on cyclic nucleotide PDE isozymes was investigated. Three PDE isozymes (PDE I, II and III) of guinea pig left ventricular muscles were used. All tested agents inhibited cyclic AMP hydrolysis by PDE III IN A concentration-dependent manner. Some agents represented more potent and selective inhibitory effect on PDE III than that of imazodan.