• Applied Biological Chemistry
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• v.43 no.2
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• pp.95-99
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• 2000

A series of hetero ring (X) substitued chalcone derivatives with farnesyl protein transferase (FPTase) inhibition activities $(pI_{50})$ values determined in vitro is analyzed by modified Free-Wilson (F-W) and Hansch method for quantitative structure activity relationship (QSARs). On the basis of F-W analysis on the FPTase inhibitory activity of a training set of the compounds, none of the (X)-substituents were not contribute the activity. But the net charge of ${\alpha}$ carbon atom is contribute the activity than that of ${\beta}$ carbon atom. And the relative orders of the (Y)-substituents on the activity are ortho>meta>para-substituents. According to Hansch approach, the activities would depend largely on the optimal, $(R_{opt.}=-0.35)$ resonance effect with ortho substituted $(I_o>0)$ electron donating group (R<0) and STERIMOL parameter, $B_1$ constant. The inhibition activity between hetro ring substituents have been a proportioned with each others and none substituent(H), 45 showed the highest FPTase inhibition $(pI_{50}=4.30)$ activity.

• BMB Reports
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• v.29 no.3
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• pp.225-229
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• 1996

Effects on thrombin by an amphipathic cation, dequalinium, which has been recognized as an anticarcinoma agent were investigated with small chromogenic substrates such as Na-benzoyl-DL-argininep-nitroanilide (BApNA), H-D-phenylalanyl-L-pipecoyl-L-arginine-p-nitroanilide (S-2238), and Na-p-tosyl-L-arginine methyl ester (TAME). Among them, only TAME hydrolysis due to an esterase activity of the enzyme was significantly activated to 81% at 20 ${\mu}M$ dequalinium in the absence of NaCl. This stimulation became even higher in the presence of 0.2 M NaCl to 3.5-fold at 60 ${\mu}M$ dequalinium. This specific activation of thrombin was well correlated with the results of in vitro coagulation tests measuring the activated partial thromboplastin time (APTT) and the prothrombin time (PT) It is pertinent. therefore, to suggest that the esterase activity should be examined in addition to the effects on 5-2238 hydrolysis when especially any regulators not directed to an active site of thrombin need to be studied. We also expect that dequalinium could be a useful tool for studying structure-function relationship of thrombin and blood coagulation.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.832-839
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• 2003

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.335-339
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• 1999

The oxidation-reduction potentials of cosmetic raw materials, showing tyrosinase inhibitory action, and phenolic compounds structurally similar to L-tyrosine were determined by cylcic voltammetry. The voltammograms obtained could be classified ito 4 patterns (patterns 1-4). Patterns 1, characterized by oxidation and reduction peaks as a pair, was observed with catechol, hydroquinone or phenol, and pattern 2 exhibiting another oxidation peak in addition to oxidation and reduction peaks as a pair was found with arbutin, kojic acid, resorcinol, methyl p-hydroxybenzoate and L-tyrosine as the substrate of tyrosinase. Pattern 3 with an independent oxidation peak only was expressed by L-ascorbic acid, and pattern 4 with a reduction peak only at high potentials, by hinokitiol. The tyrosinase inhibitory activity of these compounds was also evaluated using the 50% inhibitory concentration ($IC_{50}$) and the inhibition constant (Ki) as parameters. Hinokitiol, classified as patterns 4, showed the highest inhibitory activity (lowest $IC_{50}$ and Ki). Hydroquinone showing the second highest activity belonged to pattern 1, which also included compounds exhibiting pattern 2 was relatively low with Ki values being in the order of 10-4 M. Although there was no consistent relationship between oxidation-reduction potentials and tyrosinase inhibitory action, the voltammetry data can be used as an additional index to establish the relationship between the structure and the tyrosine inhibitory activity.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3565-3570
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• 2012

Until now, few groups reported the antifreeze activity of cyclic glycopeptides; however, the tedious synthetic procedure is not amenable to study the intensive structure activity relationship. A series of N-linked cyclic glycopeptoids and glycopeptide have been prepared to evaluate antifreeze activity as a function of peptide backbone cyclization and methyl stereochemical effect on the rigid Thr position. This study has combined the cyclization protocol with solid phase peptide synthesis and obtained significant quantities of homogeneous cyclic glycopeptide and glycopeptoids. Analysis of antifreeze activity revealed that our cyclic peptide demonstrated RI activity while cyclic glycopeptoids showed no RI activity. These results suggest that the subtle changes in conformation and Thr orientation dramatically influence RI activity of N-linked glycopeptoids.

• Journal of Ecology and Environment
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• v.34 no.4
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• pp.401-410
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• 2011

We assayed the effects of simulated acid rain on the mass loss, $CO_2$ evolution, dehydrogenase activity, and microbial biomass-C of decomposing Sorbus alnifolia leaf litter at the microcosm. The dilute sulfuric acid solution composed the simulated acid rain, and the microcosm decomposition experiment was performed at 23$^{\circ}C$ and 40% humidity. During the early decomposition stage, decomposition rate of S. alnifolia leaf litter, and microbial biomass, $CO_2$ evolution and dehydrogenase activity were inhibited at a lower pH; however, during the late decomposition stage, these characteristics were not affected by pH level. The fungal component of the microbial community was conspicuous at lower pH levels and at the late decomposition stage. Conversely, the bacterial community was most evident during the initial decomposition phase and was especially dominant at higher pH levels. These changes in microbial community structure resulting from changes in microcosm acidity suggest that pH is an important aspect in the maintenance of the decomposition process. Litter decomposition exhibited a positive, linear relationship with both microbial respiration and microbial biomass. Fungal biomass exhibited a significant, positive relationship with $CO_2$ evolution from the decaying litter. Acid rain had a significant effect on microbial biomass and microbial community structure according to acid tolerance of each microbial species. Fungal biomass and decomposition activities were not only more important at a low pH than at a high pH but also fungal activity, such as $CO_2$ evolution, was closely related with litter decomposition rate.

• Journal of the Korean Chemical Society
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• v.57 no.6
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• pp.744-754
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• 2013

Quantitative structure-activity relationship (QSAR) analysis for recently synthesized imidazole-(benz)azole and imidazole - piperazine derivatives was studied for their anticancer activities against breast (MCF-7) cell lines. The statistically significant 2D-QSAR models ($r^2=0.8901$; $q^2=0.8130$; F test = 36.4635; $r^2$ se = 0.1696; $q^2$ se = 0.12212; pred_$r^2=0.4229$; pred_$r^2$ se = 0.4606 and $r^2=0.8763$; $q^2=0.7617$; F test = 31.8737; $r^2$ se = 0.1951; $q^2$ se = 0.2708; pred_$r^2=0.4386$; pred_$r^2$ se = 0.3950) were developed using molecular design suite (VLifeMDS 4.2). The study was performed with 18 compounds (data set) using random selection and manual selection methods used for the division of the data set into training and test set. Multiple linear regression (MLR) methodology with stepwise (SW) forward-backward variable selection method was used for building the QSAR models. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by kNN-MFA, (k-Nearest Neighbor Molecular Field Analysis) investigating the substitutional requirements for the favorable anticancer activity. The results derived may be useful in further designing novel imidazole-(benz)azole and imidazole-piperazine derivatives against breast (MCF-7) cell lines prior to synthesis.

• Bulletin of the Korean Chemical Society
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• v.32 no.12
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• pp.4352-4360
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• 2011

A four dimensional quantitative structure activity relationship analysis was applied to a series of 50 flavonoid inhibitors of $p56^{lck}$ protein tyrosine kinase by the molecular comparative electron topological method. It was found that the -log (IC50) values of the compounds were highly dependent on the topology, size and electrostatic character of the substituents at seven positions of the flavonoid scaffold in this study. Depending on the negative or positive charge of the groups correctly embedded in these substituents, three-dimensional bio-structure to increase or decrease -log (IC50) values in the training set of 39 compounds was predicted. The test set of 11 compounds was used to evaluate the predictivity of the model. To generate 4D-QSAR model, the defined function groups and pharmacophore used as topological descriptors in the calculation of activity were of sufficient statistical quality ($R^2$ = 0.72 and $Q^2$ = 0.69). Ligand docking approach by using Dock 6.0. These compounds include many flavonoid analogs, They were docked onto human families of p56lck PTKs retrieved from the Protein Data Bank, 1lkl.pdb.

• Environmental Mutagens and Carcinogens
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• v.20 no.1
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• pp.21-25
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• 2000

Recently there is increasing interest in the use of structure activity relationships for predicting the biological activity of chemicals. The reasons for the interest include the decrease cost and time per chemical as compared with animal or cell system for identifying toxicological effects of chemicals and the reduction in the use of animals for toxicological testing. This study is to test the validity of the mutagenicity data generated from QSAR (Quantitative Structure Activity Relationship) program. Thirty chemicals, which had been evaluated by Ames test during 1997-1999, were assessed with TOPKAT QSAR mutagenicity prediction module. Among 30chemicals experimented, 28 were negative and 2 were positive for Ames test. On the contrary, 23 chemicals showed the high confidence level indicating high prediction rate in mutagenicity evaluation, and 7 chemicals showed the lsow to moderate confidence level indicating low prediction in mutagenicity evaluation. Overall mutagenicity prediction rate was 77% (23/30). The prediction rates for non-mutagenic chemicals were 79% (22/28) and mutagenic chemicals were 50% (1/2). QSAR could be a useful tool in providing toxicological data for newly introduced chemicals or in furnishing data for MSDS or in determining the dose in toxicity testing for chemicals with no known toxicological data.

• Bulletin of the Korean Chemical Society
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• v.26 no.6
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• pp.952-958
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• 2005

Angiotensin-converting enzyme (ACE) is known to be primarily responsible for hypertension. Threedimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA ($q^2$ = 0.530, $r^2$ = 0.998) and CoMSIA ($q^2$ = 0.518, $r^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for better activity against ACE.