• Archives of Pharmacal Research
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• v.25 no.4
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• pp.463-468
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• 2002

We have previously reported on the identification of the endogenous transmethylation inhibitor oligosaccharide-linked acyl carrier protein (O-ACP), In this study, the role of the transmethylation reaction on cell cycle progression was evaluated using various transmethylase inhibitors, including O-ACP. O-ACP significantly inhibited the growth of various cancer cell lines, including NIH3T3, ras-transformed NIH3T3, MDA-MB-231, HT-1376, and AGS. In addition, exposure of ras-transformed NIH3T3 to O-ACP caused cell cycle arrest at the $G_0/G_1$ phase, which led to a decrease in cells at the S phase, as determined by flow cytometry. In contrast, transmethylase inhibitors did not affect the expression of $p21^{WAF1/Cip1}$, a well known inhibitor of cyclin dependent kinase, indicating that the cell cycle arrest by transmethylase inhibitors might be mediated by a $p21^{WAF1/Cip1}$-independent mechanism. Therefore, O-ACP, a novel transmethylase inhibitor, could be a useful tool for elucidating the novel role of methylation in cell proliferation and cell cycle progression.

• Journal of Integrative Natural Science
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• v.7 no.1
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• pp.45-49
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• 2014

The (c-Jun N-terminal kinase 3) JNK3 is a potential therapeutic target for various neurological disorders. Here, a three dimensional quantitative structure-activity relationship (3D-QSAR) study on phenoxypyridine as JNK3 inhibitors was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The comparative molecular field analysis (CoMFA) using different partial atomic charges, was employed to understand the structural factors affecting JNK3 inhibitory potency. The Gasteiger-Marsili yielded a CoMFA model with cross-validated correlation coefficient ($q^2$) of 0.54 and non-cross-validated correlation coefficient ($r^2$) of 0.93 with five components. Furthermore, contour maps suggested that bulky substitution with oxygen atom in $R^3$ position could enhance the activity considerably. The work suggests that further chemical modifications of the compounds could lead to enhanced activity and could assist in the design of novel JNK3 inhibitors.

• Journal of Integrative Natural Science
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• v.17 no.1
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• pp.13-20
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• 2024

Female breast cancer is the fifth highest cause of mortality. Breast cancer is the most prevalent type of cancer in women globally, while it can also affect men. STAT5A plays a role in its development and progression. Given that activation of STAT5a is frequently linked to the growth and progression of tumors, STAT5a has been identified as a possible target for the therapy of several cancers. STAT5A, in particular, has proven to be overexpressed in various breast cancer cell lines and tumors, and it has been associated to the promotion of tumour cell proliferation and survival. STAT5A inhibition has been shown in vitro and in vivo to reduce the development of breast cancer cells. As a result, we have screened compounds from the FDA database that might serve as potential inhibitors of STAT5a through virtual screening, docking, DFT and MD simulation approaches. The drug Nilotinib has shown promising results inhibiting STAT5a. Further, in-vitro analysis will be carried forward to understand the anti-cancer activity.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.235.3-236
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• 2003

S-adenosyl-L-homocysteine(AdoHcy) is the product of all biological methylation in which S-adenosyl-L-methionine (AdoMet) is utilized as a methyl donor and is reversibly hydrolyzed to L-homocysteine and adenosine by AdoHcy hydrolase physiologically. Inhibition of this enzyme results in intracelluar accumulation of AdoHcy leading to a feedback inhibition of AdoMet-dependent methylation reactions which are essential for viral replication. (omitted)

• Korean Journal of Pharmacognosy
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• v.26 no.1
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• pp.62-65
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• 1995

Dopamine ${\beta}-hydroxylase$ (DBH) catalyses the enzymatic reaction of dopamine to norepinephrine. For the purpose of isolating DBH inhibitors from natural resources, thirty one kinds of medicinal plants were screened by tracing the inhibitory activities against bovine adrenal DBH, utilizing tyramine as a substrate. Among the crude drugs tested, leaves of Lactuca sativa L., Gardeniae Fructus, Magnoliae Flos and Scutellariae Radix showed potent enzyme inhibitory activities against DBH.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.145.1-145.1
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• 2003

Several lines of recent evidences have shown that several pro-inflammatory genes or mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and cytokines (e.g., tumor necrosis factor $\alpha$ and interleukin-1$\beta$), are strongly expressed in the ischemic brain. Inflammation is now recognized as a significant contributing mechanism in cerebral ischemia because anti-inflammatory compounds or inhibitors of iNOS and cyclooxygenase-2 have been proven to reduce ischemic brain damage. (omitted)

• Journal of Ecology and Environment
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• v.29 no.4
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• pp.337-342
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• 2006

The total monoterpenoid content of the pine litter layer and the availability of these compounds as inhibitors/stimulators on Polysphondylium violaceum of cellular slime molds were investigated. In order to determine the several monoterpenoids in the natural environment, we examined their concentrations in fresh, senescent, and decaying needles from 3 pine species (Pinus densiflora, P. thunbergii, P. rigida) by litter bag method. Total monoterpenoid content was highest in the fresh needles, but also remained relatively high in senescent needles. The effect of monoterpenoids identified from Pinus plants on the growth of P. violaceum was studied. We tested four concentrations (1, 0.1, 0.01, and $0.001\;{\mu}g/{\mu}L$) of each compound by using a disk volatilization technique. Each compound was treated after germination of spores of P. violaceum. All of the compounds at $1\;{\mu}g/{\mu}L$ concentration had a very strong inhibitory effect on cell growth of P. violaceum. Fenchone at all concentrations, myrcene, verbenone, bornyl acetate, and limonene at low concentrations stimulated the growth of P. violaceum. These results suggest that inhibitory or enhancing effects of selected monoterpenoids depend upon the concentration of the individual compound.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.734-737
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• 1998

The hexane fractions from methanolic extracts of Anetheum graveolens L. (Umbelliferae) and Acorus gramineus Soland. (Araceae) revealed potent inhibitory activities against the resistance of multi-drug resistant Staphylococcus aureus SA2 when combined with ampicillin (Am) or chloramphenicol (Cm). As active principles, carvone and the liquid mixture containing carvone from Anetheum graveolens L. and a liquid mixture mainly consisting of benzoic acid phenyl-methyl ester (benzyl benzoate) from Acorus gramineus Soland. were identified. They showed resistance inhibition at the level of 20-50${\mu}g$/ml when combined with 100 or ${\mu}g$/ml of Am or Cm, respectively.

• Journal of Integrative Natural Science
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• v.7 no.3
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• pp.166-172
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• 2014

Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Activation of caspases-3 stimulates a signaling pathway that ultimately leads to the death of the cell. Hence, caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage. In this work, comparative molecular field analysis (CoMFA) was performed on a series of 3, 4-dihydropyrimidoindolones derivatives which are inhibitors of caspase-3. The best predictions were obtained for CoMFA model ($q^2=0.676$, $r^2=0.990$). The predictive ability of test set ($r^2_{pred}$) was 0.688. Statistical parameters from the generated QSAR models indicated the data is well fitted and have high predictive ability. Our theoretical results could be useful to design novel and more potent caspase-3 derivatives.

• Natural Product Sciences
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• v.2 no.2
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• pp.137-142
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• 1996

This paper gives a description about the germination inhibition of American ginseng (Panax quinquefolium L.) seed coat. The existence of seed coat is one of the inhibitory factors which inhibit the embryo growth, particularly during the morphological after-ripening stage. The seed coat can obstruct the water absorption at the beginning of seed stratification, but it can not threaten seed germination. The inhibition of seed coat is not caused by the mechanical fetter neither. However, before splitting the seed coat, the inhibition of seed coat comes from both air-tight character and inhibitors, and after splitting the seed coat, the inhibition may come mainly from the inhibitors.