• Natural Product Sciences
• /
• 제10권2호
• /
• pp.80-84
• /
• 2004

Rosmarinic acid and its methyl ester, isolated from the ethyl acetate soluble fraction of the methanolic extract of Salvia miltiorrhiza Bunge (Labiatae), were found to inhibit the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with the $IC_{50}$ values of 16.8 and $21.5\;{\mu}M$, respectively. It was comparable with kojic acid, a well-known tyrosinase inhibitor, with an $IC_{50}$ of $22.4\;{\mu}M$. The inhibitory kinetics analyzed by the Lineweaver-Burk plots, were found rosmarinic acid and its methyl ester to be competitive inhibitors with $K_i\;of\;2.4{\times}10^{-5}\;and\;1.5{\times}10^{-5}\;M$, respectively.

• Archives of Pharmacal Research
• /
• 제27권11호
• /
• pp.1132-1135
• /
• 2004

In order to find new tyrosinase inhibitors and the effects of prenyl residue on flavonoid molecules, eight prenylated and three synthetic vinylated flavonoids were examined on their inhibitory effect against tyrosinase activity. From the results, kuwanon C, papyriflavonol A, sanggenon D and sophoflavescenol were found to possess the considerable inhibitory activity. Especially, sanggenon D is revealed as a potent inhibitor ($IC_{50}$ =7.3$\mu$ M), compared to the reference compound, kojic acid ($IC_{50}$ =24.8 $\mu$M). However, the prenylation with isoprenyl group or the vinylation to flavonoid molecules did not enhance tyrosinase inhibitory activity.

• 통합자연과학논문집
• /
• 제9권4호
• /
• pp.241-248
• /
• 2016

Corticotropin-releasing factor receptors (CRFRs) activate the hypothalamic-pituitary-adrenal axis, which is an integral part of the fight or flight response to stress. Increase in CRH level is observed in Alzheimer's disease and major depression and hypoglycemia. Here, we report on the relevant physicochemical parameters required for the CRFR inhibitors. Comparative molecular similarity indices analysis (CoMSIA) was performed with the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolinesas CRFR inhibitors. The best predictions were obtained for the best CoMSIA model with a $q^2$ of 0.576 with 6 components and $r^2$ of 0.977. The statistical parameters from the generated CoMSIA models indicated that the data are well fitted and have high predictive ability. CoMSIA contour maps could be useful in the designing of more potent and novel CRFR derivatives.

• 약학회지
• /
• 제43권4호
• /
• pp.509-515
• /
• 1999

To search for new chitin biosynthesis inhibitors from natural sources, several higher plants were examined the inhibitory activity against chitin synthase IIby enzymatic assay. Among them, the extract of Schizandra chinensis strongly showed the inhibitory activity against chitin synthase II. Gomisin N and wuweizisu C were isolated from Schizandra chinensis and showed $IC_50$ value of $62.4{\;}\mu\textrm{g}/ml$ and $19.2{\;}\mu\textrm{g}/ml$, respectively. Activities of these compounds were more stronger than that of polyxin D. However, gomisin N and wuweizisu C showed weakly antifungal activities against various human pathogens.

• Bulletin of the Korean Chemical Society
• /
• 제31권11호
• /
• pp.3291-3296
• /
• 2010

A gelastatins (1), natural MMP inhibitors, and their hydroxamate analogues (2) in TACE enzyme evaluated for discovery of potent TACE inhibitors. We have employed molecular dynamics simulations to compute the relative free energy of hydration and binding to TACE for gelastatin (1) and its hydroxamate analogue (2). The relative free energy difference is directly described in this article using the free energy perturbation approach as a means to accurately predict the TACE inhibitor of gelastatin analogues. The results show that the good agreement between the experimental and theoretical relative free energies of binding, gelastatin hydroxamate (2) binds stronger to TACE by -3.37 kcal/mol. The desolvation energy costs significantly reduced binding affinity, hydroxamate group associated with high desolvation energy formed strong favorable interactions with TACE with more than compensated for the solvation costs and therefore led to an improvement in relative binding affinity.

• 한국해양바이오학회지
• /
• 제2권4호
• /
• pp.230-233
• /
• 2007

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. As part of our searching for PTP1B inhibitors from natural products, the extracts of marine microorganisms were screened for the inhibitory effects on the activity of protein tyrosine phosphatase 1B (PTP1B). Among the tested 304 extracts, 29 extracts exhibited inhibition rate ranging 40.1 - 83.6 % against PTP1B at the concentration level of $30{\mu}g/mL$.

• 통합자연과학논문집
• /
• 제7권4호
• /
• pp.227-233
• /
• 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 similarity indices analysis (CoMSIA) was performed on a series of 3,4-dihydropyrimidoindolones derivatives which are inhibitors of caspase-3. The best predictions were obtained for CoMSIA model ($q^2$ = 0.586, $r^2$ = 0.955). The predictive ability of test set ($r^2_{pred}$) was 0.723. 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.

• Bulletin of the Korean Chemical Society
• /
• 제20권8호
• /
• pp.925-928
• /
• 1999

The process of transcription is the major point at which gene expression is regulated. The jun and fos families of eukaryotic transcription factor heterodimerize to form complexes capable of binding 5'-TGAGTCA-3'DNA elements (AP-1 binding site). To search for the inhibitors of the jun-fos-DNA complex formation, several natural products extracts were screened and methanol extract of tanshen (the dried roots of Salvia miltiorrhiza Bunge) showed remarkable inhibitory activity. The active compounds of the extracts were purified using re-peated column chromatography and recrystallization. Their structures were identified as tanshinone I and tanshinone IIA. Through the electrophoresis mobility shift assay and cell cytotoxicity test, tanshinone I and tanshinone IIA were identified as inhibitors that suppress not only AP-1 function but also the cell proliferation. Tanshinone I also suppressed the jun-fos-DNA complex formation in TPA-induced NIH 3T3 cells.

• 통합자연과학논문집
• /
• 제4권1호
• /
• pp.23-30
• /
• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• 통합자연과학논문집
• /
• 제5권1호
• /
• pp.6-12
• /
• 2012

c-Jun N-terminal kinase-3 (JNK-3) has been identified as a promising target for neuronal apoptosis and has the effective therapeutic for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. Herein, we report the essential structural and chemical parameters for JNK-3 inhibitors utilizing comparative molecular field similarity indices analysis (CoMSIA) using the derivatives of 3,5-disubstituted quinolines. The best predictions were obtained CoMSIA model (q2=0.834, r2=0.987) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.