• 농약과학회지
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• 제9권2호
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• pp.146-152
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• 2005

분자 홀로그램(H) QSAR 방법으로 일련의 새로운 2-alkoxyphenyl-3-phenylthioisoindoline-1-one 유도체들의 구조 변화에 따른 저항성(RPC) 및 감수성(SPC) 고추역병균주(Phytopthora capsici)에 대한 살균활성 관계를 연구하였다. 두 균주에 대한 살균활성에 관한 HQSAR 모델(RPC: RI-B 및 SPC: SII-A)들은 예측성($r^2_{cv.}$ 또는 $q^2=0.806{\sim}0.865$)과 상관성($r^2_{ncv.}=0.921{\sim}0.952$)에 근거하여 매우 높은 통계값들을 나타내었다. 이에 근거하여 HQSAR 모델들은 RPC 보다는 SPC에 대하여 양호한 살균활성을 나타내는 경향을(SPC> RPC) 보였다. 특히, atomic contribution map으로부터 RPC 균주의 선택적인 살균활성은 2-fluoro-4-chloro-5-alkoxyanilino 기에 의존적임을 확인하였다.

• Archives of Pharmacal Research
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• 제27권9호
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• pp.893-900
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• 2004

2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (％) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.154-154
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• 2002

Benzoyl peroxide is a High Production Volume Chemical, which is produced about 1,375 tons/year in Korea as of 2001 survey. The substance is mainly used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. The substance is one of seven chemicals of which human health and environmental risks are being assessed by National Institute of Environmental Research (NIER) under the frame of OECD SIDS Program. In this study, Quantitative Structure-Activity Relationships (QSAR) is used for getting adequate information on the physical-chemical property and the environmental fate of this chemical. For the assessment of benzoyl peroxide, models such as MPBPWIN for vapor pressure, KOWWIN for octanol/water partition coefficient, HENRYWIN for Henry's Law constant, AOPWIN for photolysis and BCFWN for bioconcentration factor (BCF) were used. These (Q)SAR model programmes were worked by using the SHILES (Simplified Molecular Input Line Entry System) notations. The physical-chemical properties and the environmental fate of benzoyl peroxide were estimated as followed : vapor pressure =0.00929 Pa, Log Kow = 3.43, Henry's Law constant = 0.00000354 atm-㎥/mole at 25 $^{\circ}C$, the half-life of photodegradation = 3 days, bioconcentration factor (BCF) = 92

• Bulletin of the Korean Chemical Society
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• 제32권1호
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• pp.251-262
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• 2011

Human ether-a-go-go related gene (hERG) potassium channel blockade, an undesirable side effect which might cause sudden cardiac death, is one of the major concerns facing the pharmaceutical industry. The purpose of this study is to develop an in silico QSAR model which uncovers the structural parameters of T-type calcium channel blockers to reduce hERG blockade. Comparative molecular similarity indices analysis (CoMSIA) was conducted on a series of piperazine and benzimidazole derivatives bearing methyl 5-(ethyl(methyl)amino)-2-isopropyl-2-phenylpentanoate moieties, which was synthesized by our group. Three different alignment methods were applied to obtain a reliable model: ligand based alignment, pharmacophore based alignment, and receptor guided alignment. The CoMSIA model with receptor guided alignment yielded the best results : $r^2$ = 0.955, $q^2$ = 0.781, $r^2_{pred}$ = 0.758. The generated CoMSIA contour maps using electrostatic, hydrophobic, H-bond donor, and acceptor fields explain well the structural requirements for hERG nonblockers and also correlate with the lipophilic potential map of the hERG channel pore.

• Interdisciplinary Bio Central
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• 제3권4호
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• pp.15.1-15.11
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• 2011

Background: Histone deacetylase (HDAC) 8 is one of its family members catalyzes the removal of acetyl groups from N-terminal lysine residues of histone proteins thereby restricts transcription factors from being expressed. Inhibition of HDAC8 has become an emerging and effective anti-cancer therapy for various cancers. Application computational methodologies may result in identifying the key components that can be used in developing future potent HDAC8 inhibitors. Results: Facilitating the discovery of novel and potential chemical scaffolds as starting points in the future HDAC8 inhibitor design, quantitative structure-activity relationship models were generated with 30 training set compounds using genetic function approximation (GFA) and Bayesian algorithms. Six GFA models were selected based on the significant statistical parameters calculated during model development. A Bayesian model using fingerprints was developed with a receiver operating characteristic curve cross-validation value of 0.902. An external test set of 54 diverse compounds was used in validating the models. Conclusions: Finally two out of six models based on their predictive ability over the test set compounds were selected as final GFA models. The Bayesian model has displayed a high classifying ability with the same test set compounds and the positively and negatively contributing molecular fingerprints were also unveiled by the model. The effectively contributing physicochemical properties and molecular fingerprints from a set of known HDAC8 inhibitors were identified and can be used in designing future HDAC8 inhibitors.

• Bulletin of the Korean Chemical Society
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• 제30권3호
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• pp.613-617
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• 2009

3D-QSARs for the inhibition activities against protox by herbicidal 2-N-phenylisoindolin-1-one derivatives were studied quantitatively using CoMFA and CoMSIA methods. The result of the statistical quality of optimized CoMSIA model 2 ($FF:\;{r^2}_{cv.};\;0.973\;&\;{r^2}_{ncv.};\;0.612$) was higher than that of CoMFA model 1 ($AF:\;{r^2}_{cv.};\;0.414\;&\;{r^2}_{ncv.};\;0.909$). Also, the relative contribution of the optimized CoMSIA model 2 showed the steric (24.6%), electrostatic (31.0%), hydrophobic (ClogP, 23.4%) and H-bond acceptor field (21.0%), respectively. From the results of the contour maps, the protox inhibition activities are expected to increase when steric favor and H-bond acceptor favor groups are substituted on $R_2$ position and positive favor group are substituted on $C_2,\;C_3,\;and\;C_5$ atom in phenyl ring of $R_2$ position. And the inhibition activities are expected to increase when hydrophobic favor group is substituted on $C_1,\;C_3$ atom in phenyl ring of $R_2$ position and $C_1$ atom of $R_2$ position and hydrophilic favor groups are substituted on $C_4$ atom in phenyl ring of $R_1$ position and the terminal group of $R_1$ position.

• 약학회지
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• 제54권5호
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• pp.328-333
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• 2010

Comparative molecular field analyses (CoMFA) on the antiproliferative activity of N-substituted (R) 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole analogues (ADTs: 1-17) against bladder cancer (HCV29T) and rectal cancer (SW707) cells were studied quantitatively. The statistical predictability and fitness of CoMFA A1 model for bladder cancer cells were better than those of CoMFA F1 model for rectal cancer cells and the antiproliferative activity of ADTs depends on steric field (HCV29T: 93.1% & SW707: 83.8%). Also, from the contour maps of optimized CoMFA models, the activity for bladder cancer cells had predicted to increase when sterically favored groups were substituted on meta- and para-position, and sterically disfavored groups were substituted on one ortho-position of phenyl ring. The activity for rectal cancer cells had predicted to increase when sterically favored groups were substituted on para-position, and sterically disfavored groups were substituted on two ortho-position of phenyl ring as R-group.

• 농약과학회지
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• 제11권3호
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• pp.138-143
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• 2007

감수성(SBC) 및 저항성(RBC) 잿빛곰팡이병균(Botrytis cinerea)에 대한 N-phenyl-O-phenylthionocarbamate 유도체들의 선택적인 살균활성에 대한 3차원적인 구조와 활성과의 관계(3D-QSAR)를 CoMFA와 CoMSIA 방법으로 검토하였다 그 결과, 통계적으로 CoMFA 모델(M5)보다 CoMSIA 모델(M7)이 양호하였으며 살균활성의 선택성에 미치는 요소는 CoMSIA 모델(M7)의 정전기장에 의존적이었다. 그러므로 CoMSIA 모델(M7)의 등고도로부터 N-phenyl 고리의 meta-위치에 음하전을 띄는 수소결합 주게에 의하여 선택성이 개선될 것으로 예상되었다.

• Applied Biological Chemistry
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• 제35권5호
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• pp.382-388
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• 1992

N-치환 phenyl-5-chloro-1,3-dimethylpyrazole-4-carboxamide 45종을 합성, Rhizoctonia solani에 대한 50% 균사생육저해율$(EC_{50})$을 검정한 후 구조활성상관관계를 규명하기 위해 화합물의 소수성 파라메타인 log k', 치환기의 소수성 파라메타 ${\pi}$, 전자적 파라메타인 Hammett 치환상수 ${\sigma}$ 및 입체적 파라메타인 STERIMOL 상수 L을 사용하여 다중회귀식을 도출하였다(식(8)). 이 식에 의해 83%의 생리활성변화가 유의성있게 해석되었으며 활성에 영향을 미치는 가장 중요한 인자는 화합물의 체내흡수 및 작용점으로의 이행에 관여하는 log k'으로 밝혀졌고 그 밖에 phenyl고리의 2번위치와 3번위치 치환기의 장축을 표현하는 입체적 파라메타인 $L_3$과 $L_4$등도 활성을 지배하는 인자로 확인되었다.

• 농약과학회지
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• 제5권3호
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• pp.12-17
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• 2001

5-Benzofuryl-2-[1-(alkoxyimine) alkyl]-3-hydroxycyclohex-2-en-1-one 유도체중에서 2,3-dihydro-2,3,4,6,7-penta-methylbenzofuran-5-yl 그룹이 치완된 화합물(III)들의 벼(직파 및 3엽기)와 강피(Echinochloa crus-galli)에 대한 제초활성을 측정하고 alkoxy-치환체($OR_2$)가 변화함에 따른 구조와 제초활성과의 관계(SAR)를 정량적으로 검토한 결과, 직파벼와 강피 사이의 선택성 조건은 $R_1$=ethyl-이고 $R_2$-기는 비 대칭성의 적정값$(L/B_1)_{opt.}=3.96{\AA}$에 가까운 값을 갖는 치환체 이어야 할 것으로 판단되었다. 그리고 Free-Wilson 분석에 따르면 $R_2$-기는 $C_1{\sim}C_3$의 주로 불포화된 것들 중에서 특히, 3-chloro-2-propenyl기가 강피에 대한 제초활성을 가장 크게 나타내었다.