• Journal of Integrative Natural Science
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• v.4 no.3
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• pp.210-215
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• 2011

Holographic quantitative structure-activity relationships (HQSAR) is a useful tool to correlates structures with their biological activities. HQSAR is a two dimensional (2D) QSAR methodology, which generates QSAR equations through 2D fingerprint and correlates it with biological activity. Here, we report a 2D-QSAR model for a series of fifty-one 3,4-dihydroxychalcones derivatives utilizing HQSAR methodology. We developed HQSAR model with 6 optimum numbers of components (ONC), which resulted in cross-validated correlation coefficient ($q^2$) of 0.855 with 0.283 standard error of estimate (SEE). The non-cross-validated correlation coefficient (r2) with 0.966 indicates the model is predictive enough for analysis. Developed HQSAR model was binned in to a hologram length of 257. Atomic contribution map revealed the importance of dihydroxy substitution on phenyl ring.

• Applied Biological Chemistry
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• v.47 no.3
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• pp.351-356
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• 2004

Holographic quantitative structure activity relationships (HQSAR) as 2D QSAR between the herbicidal activities against root and shoot of rice plant (Orysa sativa L.) and barnyardgrass (Echinochloa crus-galli), and structures of A=3,4,5,6-tetra-hydrophthalimino, B = 3-chloro-4,5,6,7-tetrahydro-2H-indazolyl and C = 3,4-dimethylmaleimino substituents in 1-(5-methyl-3-phenylisoxazolin-5-yl)methoxy-2-chloro-4-fluorobenzene derivatives were studied and discussed. The statistical results of four HQSAR models for the herbicidal activities against root and shoot of the two plants showed the best predictability of the herbicidal activities based on the cross-validated $r^2\;_{cv}\;(q^2=\;0.760{\sim}0.924)$, non cross-validated conventional coefficient $(r^2\;_{ncv}\;=\;0.868{\sim}0.970)$ and PRESS values $(0.123{\sim}0.261)$. The results indicated that the qualities of HQSAR models for barnyardgrass were slightly higher than that of rice plant. And also, the predictability of HQSAR models were higher $(q^2\;=\;HQSAR\;>\;CoMFA)$ than CoMFA but the conventional coefficients of HQSAR models lower $(r^2\;=\;HQSAR\;<\;CoMFA)$ than CoMFA. Moreover, from the contribution maps, it was founded that the selectivity between the two plants depends upon the 2-fluoro-4-chloro-5-alkoxyanilino and $R_3$ substituent on the C-phenyl ring. These features suggest where to modify a molecular structure in order to improve its selective of herbicidal activities against barnyardgrass.

• Applied Biological Chemistry
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• v.50 no.2
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• pp.127-131
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• 2007

The molecular design and holographic (H) quantitative structure-activity relationships (HQSARs) on the binding affinity constants between new 3-benzylidenemyosmine analogues and nicotin acetylcholine receptors (nAChRs) of American cockroach (Periplaneta. americana L.) were studied quantitatively. The optimized HQSAR model (IV-2) for the binding affinity constants was derived from fragment distinction of hydrogene atoms in fragment size, 5${\sim}$8 bin. The statistical results of the HQSAR model (IVI-2) exhibited the best predictability and fitness for the binding affinity constants based on the cross-validated value (q$^2$=0.507) and non cross-validated value (r$^2_{nev.}$=0.944). From the graphical analyses of atomic contribution maps, it was revealed that the binding affinity constants depends upon the anabaseine ring in molecule and the most active compounds were designed by optimized HQSAR model (VI-2).

• The Korean Journal of Pesticide Science
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• v.11 no.2
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• pp.72-81
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• 2007

Quantitative structure-activity relationships (QSARs) on the pre-emergency herbicidal activity and reactivity of a series of new O,O-dialkyl-1-phenoxyacetoxy-1-methylphosphonates (S) analogues against seed of cucumber (Cucumus Sativa) were discussed quantitatively using 2D-QSAR and HQSAR methods. The statistical values of HQSAR model were better than that of 2D-QSAR model. From the frontier molecular orbital (FMO) interaction between substrate molecule (S) and $BH^+$ ion (I) in PDH enzyme, the electrophilic reaction was superior in reactivity. From the effect of substituents, $R_2$-groups in substrate molecule (S) contributed to electrophilic reaction with carbonyl oxygen atom while X, Y-groups contributed to nucleophilic reaction with carbonyl carbon atom. And the influence of X,Y-groups was more effective than that of $R_2$-groups. As a results of 2D-QSAR model (I & II) and atomic contribution maps with HQSAR model, the more length of X, Y-groups is longer, the more herbicidal activity tends to increased. And also, the optimal ${\epsilon}LUMO$ energy, $({\epsilon}LUMO)_{opt.}$=-0.479 (e.v.) of substrate molecule is important factor in determining the herbicidal activity. It is predicted that the herbicidal activity proceeds through a nucleophilic reaction. From the analytical results of 2D-QSAR and HQSAR model, it is suggested that the structural distinctions and descriptors that contribute to herbicidal activities will be able to applied new herbicide design.

• The Korean Journal of Pesticide Science
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• v.9 no.4
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• pp.279-286
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• 2005

The herbicidal activities against pre-emergence barnyard grass (Echinochloa crus-galli) by a series of new 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpopionamide derivatives as substrate molecule were studied using molecular holographic (H) quantitative structure activity relationships (HQSAR) methodology. From the based on the findings, the higher herbicidal active compounds are predicted by the derived HQSAR model. The best HQSAR model (VI-1) was derived from fragment distinction combination of atoms/bonds in fragment size, $7{\sim}10$bin. The herbicidal activities from atomic contribution maps showed that the activity will be able to increased according to the R-substituents variation of the N-phenyl ring and change of 6-chloro-2-benzoxazolyloxy group. Based on the results, the statistical results of the best HQSAR model (VI-1) exhibited the best pedictability and fitness for the herbicidal activities based on the cross-validated value ($q^2=0.646$) and non cross-validated value ($r^2_{ncv.}=0.917$), respectively. From the graphical analyses of atomic contribution maps, it was revealed that the lowest herbicidal activitics depends upon the 4-(6-chloro-2-benzoxazolyloxy)phenoxy group ($pred.pI_{50}=-3.20$). Particularly, the R=4-fluoro, X=isobutoxy substituent (P2) of (X)-phenoxy-N-(R)-phenylpropionamide derivative is predicted as the highest active compound ($pred.pI_{50}=9.12$).

• The Korean Journal of Pesticide Science
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• v.12 no.1
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• pp.9-17
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• 2008

QSARs (Quantitative structure-activity relationships) between a series of new cyclohexanedione derivatives (5-benzofuryl-2-[1-(alkoxyimino)-alkyl]-3-hydroxycyclohex-2-en-1-ones) and their herbicidal activity against Rice plant (Oryza sativa L.) and Barnyard grass (Echinochloa crus-galli.) were discussed quantitatively using 2D-QSAR and holographic (H) QSAR methods. Generally, the HQSAR models have better predictability and fitness than the 2D-QSAR models. The herbicidal activities against Barnyard grass with 2D-QSAR II model were dependent upon Balaban indice (BI) of molecule and hydrophobicity of $R_1$ and $R_3$ group. And also, the $R_3=ethyl$ group, according to the information of the optimized HQSAR IV model, was more contribute to the herbicidal activities against Rice plant, while the 5-(cyclohex-3-enyl)-2,3-dihydrobenzofuran ring part was not contribute to the herbicidal activities against two plants.

• The Korean Journal of Pesticide Science
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• v.9 no.2
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• pp.146-152
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• 2005

The fungicidal activities against resistance phytophthora blight (RPC; 95CC7303) and sensitive phytophthora blight (Phytopthora capsici) (SPC; 95CC7105) by new 2-alkoxyphenyl-3-phenylthioisoindoline-1-one derivatives (A & B) were studied using molecular holographic quantitative structure activity relationships (HQSAR) methodology. Based on the results, the statistical results of the two best HQSAR models, RI-B for RPC and SII-A for SPC exhibited the best predictability and fitness for the fungicidal activities based on the cross-validated value ($q^2=0.806{\sim}0.865$) and non cross-validated value ($r^2_{ncv.}=0.921{\sim}0.952$, respectively. The quality of the model for SPC was slightly than that of RPC. From the based graphical analyses of atomic contribution maps, it was confirmed that the novel selective character for fungicidal activities against RPC depends upon the 2-fluoro-4-chloro-5-alkoxyanilino group.

• The Korean Journal of Pesticide Science
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• v.7 no.2
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• pp.108-116
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• 2003

A series of new quinclorac family, herbicidal 3-phenyl-5-(3,7-dichloro-8-quinolinyl)-1,2,4-oxadiazole derivatives as substrate were synthesized and their growth inhibition activity $(pI_{50})$ against root and shoot of rice plant (Oryza sativa L.) and barnyard grass (Echinochloa crus-galli) were determined. And then comparative molecular field analysis (CoMFA) and molecular holographic quantitative structure- activity relationship (HQSAR) were compared in terms of their potential for predictiability. The statistical results were suggested that HQSAR based model had better predictability than CoMFA model. The selective factors to remove barnyard grass take electron withdrawing groups which can be created positive charge and steric bulky on the phenyl ring. Results revealed that the unknown 2,6-dichloro-substituent, U5 and 2,4,6-trichloro-substituent, U6(${\Delta}pI_{50}$=CoMFA: 1.18 & HQSAR: 1.82) were predicted as compound with higher activity and selectivity.

• The Korean Journal of Pesticide Science
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• v.6 no.3
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• pp.209-217
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• 2002

Two different QSAR methods, the comparative molecular similarity indices analyses (CoMSIA) and hologram quantitative structure activity relationship (HQSAR) are studied for the fungicidal activities ($pI_{50}$) of 2-N-benzyl-5-phenoxy-3-isothiazolone derivatives against sensitive (SPC: 95CC7105) and resisitive (RPC: 95CC7303) phytophthora blight fungus (Phytaphthora capsici). According to the findings from these QSAR investigation, the cross-validation value, $q^2$ and Pearson correlation coefficient, $r^2$ in the two methods were CoMSIA: RPC; $q^2=0.675,\;r^2=0.942$, SPC; $q^2=0.350,\;r^2=0.876$ and HQSAR: RPC; $q^2=0.519,\;r^2=0.869$, SPC; $q^2=0.483,\;r^2=0.990$, respectively. Therefore, the two models of comparative statistical significance were obtained. From the CoMSIA contour maps, the important factors for selective fungicidal activity against RPC are to be expected that the lower hydrophobic and not bulkiness substituent as hydrogen bonding acceptor have to introduce to meta and para-position (C1-C6) on the phenoxy moiety. And the results of prediction suggest that HQSAR method showed higher fungicidal activity than CoMSIA method.

• Bulletin of the Korean Chemical Society
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• v.27 no.10
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• pp.1531-1536
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• 2006

Microsomal prostaglandin $E_2$ synthase (mPGES-1) is an enzyme that is associated with inflammation, pain, fever and cancer. Hologram quantitative structure activity relationship (HQSAR) was conducted on the series of MK-886 compounds acting as mPGES-1 inhibitors. A training set with 24 compounds was used to establish the HQSAR model. The best model was chosen based on the cross-validated correlation coefficient ($q^2$=0.884) and the correlation coefficient($r^2$=0.976). The model was utilized to predict the activity of the eight-test set of compounds giving the predictive $r^2$ value of 0.845. The descriptors of the model are based on fragment distinction (atoms, bond and connectivity) and fragment size (2-5 atoms). The atomic contribution maps generated from HQSAR were useful in identifying the important structural features responsible for the inhibitory activity of MK-886 inhibitors. Based on the generated model, the presence of hydrophobic biphenyl group seems to enhance inhibition of mPGES-1 that is in agreement with the previous experiments. In addition, it seems important for a halogen to be substituted to the biphenyl ring and for an acyl group to be attached to the indole moiety for enhanced activity.