• 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.

• Applied Biological Chemistry
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• v.42 no.3
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• pp.252-255
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• 1999

Inhibition activities$(pI_{50})$ of chalcone derivatives as substrate with farnesyl protein transferase(FPTase) were determined in vitro. The structure activity relationships(SAR) between the activity and physicochemical parameters of X & Y-substituents on the phenyl groups were analyzed by Free-Wilson and Hansch method. X-substituents on the benzoyl group have the more important role to inhibition activity than Y-substituents on the styryl group. Among them, none substituent, 8 showed the highest FPTase inhibition activity$(pI_{50}=4.30)$. Particularly, the SAR equation could be formulated, showing a parabolic relationship between the activity and hydrophobicity(logP) where the optimal value$({\Sigma}logP)_{opt}$ was 3.915. And also the activity depends on the steric effect(Es > 0) with X-substituent and the resonance effect(R < 0) with electron donating Y-substituents. Based on the results of SAR analyses, the interactions between substrates and receptor, FPTase, could be assumed.

• Applied Biological Chemistry
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• v.42 no.1
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• pp.68-72
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• 1999

The cytotoxicity of 1,3-diphenylpropenone derivatives known to inhibit the farnesyl protein transferase (FPTase) was examined against various established tumor cell line, A549 (lung cancer), SKMEL-2 (uterine cancer), HCT-15 (skin cancer), SKOV-3 (brain cancer) and XF-498 (colon cancer) of the 1,3-diphenylpropenone derivatives showing farnesyl protein transferase (FPTase) inhibition activity. And the structure-activity relationship (SAR) between structure of 1,3-diphenylpropenone derivatives as substrate and cytotoxicity was investigated by Free-Wilson analysis as well as Hansch method with tumor cell lines. From the result of Free-Wilson analyses, X-substituents on the benzoyl group have a more important role than Y-substituents on the styryl group. The 2,4-dichloro substituent, 15 and 2,4-dimethyl substituent, 16 showed the highest cytotoxicity (average pI_(50)=5.0). Particulary, the cytotoxicity of X-substituents increased with electronic effect $({\sigma})$ due to weak electron withdrawing group with optimum value $({\sigma}_{opt}=0.22{\sim}0.29})$ whereas that of Y-substituent resulted from various factors such as logP, $B_1$ and R constant.

• Applied Biological Chemistry
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• v.43 no.1
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• pp.52-56
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• 2000

The influence of the 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenyl- propionamide derivatives on the herbicide activities against rice plant with pre-emergence and post-emergence in down land were examined and the structure activity relationship (SAR) were analyzed by Free-Wilson and Hansch method. In pre-emergence, the SAR approach is shown that the optimal, $({\pi})_{opt}=0.91$, hydrophobicity with electron donating effect of the ortho substituted mono substituents and 2,3,4-substituted three substituents were found to be contribute the herbicidal activity. Whereas, in post-emergence, the optimal, ({\pi})_{opt}=0.50$, hydrophobicity with electron withdrawing effect of meta substituted mono subsituents and 2,3-substituted two substituents were found to be contribute the herbicide activity. The herbicide activities with post-emergence more increase than that of pre-emergence. It is assumed from the SAR equations that the 2-methyl-3-methoxy-4-cyano group substituent is selected as the most lowest herbicide activity against rice plant with post-emergence in green house. The hydrolysis reaction was proceeded through nucleophilic addition-elimination (Ad_{Nu-E})$ with the orbital control between LUMO of substrate and HOMO of water molecule. And molecular electrostatic potential (MEP) of none (H) substituent was discussed.

• The Korean Journal of Pesticide Science
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• v.3 no.3
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• pp.11-19
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• 1999

A some of synthesized 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenyl propionamide derivativesa substrates were found to selectivity significantly with both rice plant (Oryza sativa L.) and barnyard grass (Echinochloa crus-galli) for those her- bicidal activities with post emergence in up land. The selectivity of substrates against rice plant better than that of Fenoxaprop-ethyl. The structure activity relationship (SAR) n the selectivity of N-phenyl substituents were analyzed by the Free-Wilson and Hansch method. The SAR approach against barnyard grass is shown that the optimal ($({\pi})_{opt.}=1.60$) hydrophobicity and electron donating effects ($0<{\sigma}$ & 0$(ES)_{opt.}=0.87$) so that the herbicidal activity against rice plant can be decreased. The significance of these results on the selectivity between barnyard grass and rice plant is discussed. And it is assumed that the 2-ethoxy-3-methoxy-4-dimethylamino group substituent ($pI_{50}$=6.60, 1g/ha) is selected as the most highest herbicidal activity against barngard grass in green house.

• The Korean Journal of Pesticide Science
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• v.4 no.2
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• pp.21-28
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• 2000

A new fourty six 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpro- pionamide derivatives were synthesized and the herbicidal activities against rice plant and barnyard grass with pre-emergence in down land were measured. The structure activity relationships (SAR) between the activities and physicochemical parameters of the substituted(X) N-phenyl group in substrates were analyzed and discussed by Free- Wilson and Hansch method from the basis on the former study (Sung. et. al., 1999). The conditions of selective herbicide activity both the barnyard grass and rice plant are shown that the optimal hydrophobicity, $({\pi})_{opt.}=1.34$ and electron donating with field effect (F<0) of meta and ortho, para-substituted mono or disubstituent on the N-phenyl ring were found to contribute significantly. The herbicidal activities against barnyard grass are roughly the same as the results in up land whereas damage to rice plant in down land more increase than that of up land. Degradation products in water are 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)propionic acid ((A)) (obs. pKa=4.35 & obs. logP=4.77) and 6-chloro-2-benzoxazolone (B) (obs. pKa=8.40 & obs. logP=2.90). These results were supposing that the hydrolysis product of substrates, (A) is comparatively absorbed in rice plant but not in barnyard grass. And it is assumed from the SAR equations that the 2,6-dimethyl-4-methoxymethyl group substituent ($pI_{50}=5.41$, 3g/ha) is selected as the most highest herbicidal activity against barnyard grass in green house.

• The Korean Journal of Pesticide Science
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• v.6 no.4
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• pp.279-286
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• 2002

To improve the growth inhibition activities and selectivities for quinclorac family, novel 3-substituted phenyl-5-(3,7-dichloro-8-quinolinyl)-1,2,4-oxadiazole derivatives as the substrate were synthesized and their the activities ($pI_{50}$) against shoot and root of rice plant (Oryza sativa L.) and barn-yard grass (Echinochloa crus-galli) were measured. And the quantitative structure-activity relationships (QSARs) between physicochemical parameters of the substitutents (R) on phenyl group and the activities ($pI_{50}$) were analyzed quantitatively. According to the SAR analyses, the substrates of planar conformation showed higher herbicidal activities against barnyard grass than rice plant. The activities against rice plant depend on the electronic effect (shoots: ${\sigma}_{opt.}=0.49$ & root: $R_{opt.}=-0.15$) of substituents, whereas the activities against shoots and roots of barnyard grass depend on hydrophobicity (${\pi}_{opt.}=0.37{\sim}2.40$). There were conditions of selective growth inhibition activity against barnyard grass when such a ortho-substituted electron donating substituents showing the hydrophobicity value, ${\pi}=2.40$ were introduced on the phenyl ring. The 2-tolyl substituent predicted from SAR equations was expected to have better growth inhibition activity and selectivity (${\Delta}pI_{50}=1.26$) for barnyard grass.