Flavopiridol 유도체에 의한 유방암 MCF-7 세포의 저해 활성에 관한 구조와 활성과의 관계 = QSAR on the Inhibition Acticity of Flavopiridol Analogues against Breast Cancer MCF-7

다국어 초록 (Multilingual Abstract)

To search for a molecular design of a new breast cancerous inhibitory active compound, 2D-QSAR and HQSAR between the substituents of flavopiridol analogues as substrates and their breast cancerous inhibitory activities against MCF-7 cell were analyzed and discussed quantitatively. It was found that the dispersion with molecule and steric hindrance with substituents will have a tremendous impact on the inhibitory activities from the 2D-QSAR model (1). Also, MR constant is better than that of MS constant as animportant factor. The inhibitory activities from 2D-QSAR model (2) were dependent upon the optimum MR constant (MR = 126 $Cm^3/mol$). Optimized HQSAR model (V) exhibited the best predictability of the inhibitory activities based on the cross-validated $r^2_{cv}$($q^2$= 0.583) and non-cross-validated conventional coefficient ($r^2_{ncv}$= 0.982). From the contribution maps, the inhibitory activity by the imino group on $C_9$ atom was higher than that of the hydroxyl group of $C_8$ atom on the A ring in molecule. Therefore, we can confirm that the dispersion by substituents in molecule is the most important factor in inhibitory activities against MCF-7 cell.

국문 초록 (Abstract)

새로운 유방암의 억제 물질을 탐색하고 설계하기 위하여 flavopiridol 유도체의 치환기($R_1{\sim}R_2$) 변화에 따른 유방암 유발세포 MCF-7의 저해활성에 관한 2D-QSAR 및 분자 홀로그래피적인 QSAR을 분석하였다. 2D-QSAR 모델(1)로부터 분자는 분산력으로 그리고 치환기는 입체장애를 유발하는 요인으로 작용하였으며 질량(MS)보다 굴절율(MR)상수가 저해활성에 크게 기여하였다. 그리고 2D-QSAR 모델(2)로부터는 MR상수의 적정값. $(MR)_{opt.}$= 126$Cm^3/mol$을 가지는 치환기의 저해활성이 가장 높을 것으로 예상되었다. 또한, 최적의 HQSAR 모델은 분자 조각의 크기($7{\sim}10$) 조건에서 예측성($q^2$= 0.583)과 상관성($r^2$= 0.982)이 매우 양호하였으며 기여도로부터 flavopiridol 분자내 A고리의 $C_8$원자에 결합된 수소원자나 hydroxyl-기보다 $C_9$원자 부분의 imino 골격이 저해활성에 기여하였다. 결과적으로 치환기들에 의한 분산력이 유방암 유발 세포 MCF-7의 저해활성에 크게 관여하는 주요인이었다.

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