• 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.

• The Korean Journal of Pesticide Science
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• v.3 no.1
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• pp.29-36
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• 1999

A series of N-phenyl-O-phenylthionocarbamate derivatives were synthesized and determinated fungicidal activities in vitro against gray mold (Botrytis cinerea) and capsicum phytophthora blight (Phytophthora capsici) which showed resistance and sensitivity to benomyl and metalaxyl as systemic fungicides, respectively. The structure-activity relationship (SAR) was investigated by Free-Wilson analysis method and Hansch method. From the basis on the findings, the N-phenyl(X) groups had more contributions than O-phenyl(Y) groups did and ortho-substituents on the N-phenyl group showed high fungicidal activities. Especially, 4-cyano substituent, 2 as X-group showed 50% inhibition($pI_{50}=5.50$) of hyphae growth at 0.8ppm against resistance P. capsici (RPC) And hydroxyl substituents, 12 and 23 displayed the highest fungicidal activity against resistant B. cinerea (RBC), sensitive B. cinerea (SBC), and sensitive P. capsici (SPC). Antifungal activities of SPC were dependent upon molar refractivity (MR) constant and those of others relied on hydrophobic parameters (${\sigma}$ and logP). For increasing fungicidal activity against RPC and SBC, the optimum values of the sigma (${\sigma}$) and field(F) constants as electron withdrawing groups were 0.32 and 0.18, respectively.