• 약학회지
• /
• 제55권2호
• /
• pp.154-159
• /
• 2011

During the search for a novel compound that can inhibit NF-${\kappa}B$ activation, 6-hydroxy-7-methoxychroman-2-carboxylic acid phenyl amide (KL-1156) was identified as a good inhibitor of NF-${\kappa}B$ activation. In the present study, we describe the synthesis of methylchroman-2-carboxylic acid N-(disubstituted)phenylamide derivatives (1 and 2 serieses). In addition, their inhibitory effects of NF-${\kappa}B$ are compared with activity of KL-1156 and SAR (structure activity relationship) are explored.

• Bulletin of the Korean Chemical Society
• /
• 제35권7호
• /
• pp.2065-2071
• /
• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• Journal of Microbiology and Biotechnology
• /
• 제11권4호
• /
• pp.663-667
• /
• 2001

A new secondary metabolite was isolated from the culture broth and mycelium of Streptomyces sp. collected from marine sediment. The structure of this compound was determined to be N-formylantimycic acid methyl ester, an acyclic derivative of antimycin, on the basis of combined chemical and spectral methods. The structure-activity relationship of antimycins is discussed.

• Bulletin of the Korean Chemical Society
• /
• 제30권11호
• /
• pp.2717-2722
• /
• 2009

The use of the classification and regression tree (CART) methodology was studied in a quantitative structure-activity relationship (QSAR) context on a data set consisting of the binding affinities of 39 imidazobenzodiazepines for the α1 benzodiazepine receptor. The 3-D structures of these compounds were optimized using HyperChem software with semiempirical AM1 optimization method. After optimization a set of 1481 zero-to three-dimentional descriptors was calculated for each molecule in the data set. The response (dependent variable) in the tree model consisted of the binding affinities of drugs. Three descriptors (two topological and one 3D-Morse descriptors) were applied in the final tree structure to describe the binding affinities. The mean relative error percent for the data set is 3.20%, compared with a previous model with mean relative error percent of 6.63%. To evaluate the predictive power of CART cross validation method was also performed.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.123.3-124
• /
• 2003

To investigate the relationship between structure and biological activity of phenylpropanoids, we measured effects of phenylpropanoids on anti-oxidant and whitening activity. In DPPH radical scavenging activity, caffeic acid analogues had anti-oxidant activity in a dose-dependent manner. Although phenylpropanoids did not inhibit purified tyrosinase activity, they significantly inhibited tyrosinase activity and melanin production in MSH-stimulated B16 melanoma cells. (omitted)

• 한국환경독성학회:학술대회논문집
• /
• 한국환경독성학회 1998년도 추계 학술대회 발표 논문집
• /
• pp.75-75
• /
• 1998

• 미생물과산업
• /
• 제31권1호
• /
• pp.4-14
• /
• 2005

• Molecular & Cellular Toxicology
• /
• 제4권2호
• /
• pp.170-176
• /
• 2008

The quantitative structure-activity relationship (QSAR) of a set of 35 flavonoid compounds presenting antioxidant activity was established by means of Genetic Algorithm-Multiple Linear Regression (GA-MLR) technique. Four-parametric models for two sets of data, the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity $(R^2=0.788,\;Q^2_{cv}=0.699\;and\;Q^2_{ext}=0.577)$ and scavenging activity of reactive oxgen species (ROS) induced by $H_2O_2 (R^=0.829,\;Q^2_{cv}=0.754\;and\;Q^2_{ext}=0.573)$ were obtained with low external predictive ability on a mass basis, respectively. Each model gave some different mechanistic aspects of the flavonoid compounds tested in terms of the radical scavenging activity. Topological charge, H-bonding complex and deprotonation processes were likely to be involved in the radical scavenging activity.

• The Korean Journal of Physiology and Pharmacology
• /
• 제13권6호
• /
• pp.511-516
• /
• 2009

A series of substituted 2-arylnaphthyridin-4-one analogues, which were previously synthesized in our laboratory, were evaluated for their in vitro cytotoxic activity against human lung cancer A549 and human renal cancer Caki-2 cells using MTT assay. Some compounds (11, 12, and 13) showed stronger cytotoxicity than colchicine against both tumor cell lines, and compound 13 exhibited the most potent activity with $IC_{50}$ values of 2.3 and $13.4\;{\mu}M$, respectively. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Predictive 3D-QSAR models were obtained with $q^2$ values of 0.869 and 0.872 and $r^2_{ncv}$ values of 0.983 and 0.993 for CoMFA and CoMSIA, respectively. These results demonstrate that CoMFA and CoMSIA models could be reliably used in the design of novel cytotoxic agents.

• Bulletin of the Korean Chemical Society
• /
• 제27권2호
• /
• pp.266-272
• /
• 2006

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.