化学通报（网络版）
化學通報（網絡版）
화학통보（망락판）
Chemistry Online
2015年
8期
1-9
,共9页
吴建军%马玉卓%戴雪娥%刘鹰翔
吳建軍%馬玉卓%戴雪娥%劉鷹翔
오건군%마옥탁%대설아%류응상
3-氨磺酰基苯甲酸衍生物%AKR1C3抑制剂%分子对接%COMFA%COMSIA
3-氨磺酰基苯甲痠衍生物%AKR1C3抑製劑%分子對接%COMFA%COMSIA
3-안광선기분갑산연생물%AKR1C3억제제%분자대접%COMFA%COMSIA
3-sulfamoylbenzoic acid derivatives%AKR1C3 inhibitors%Molecular docking%COMFA%COMSIA
醛酮还原酶1C3(AKR1C3)作为治疗前列腺癌的新靶点已成为研究热点，3-氨磺酰苯甲酸衍生物对其具有高效的选择性和抑制活性。本文采用比较分子场分析(COMFA)和比较分子相似性指数分析(COMSIA)方法，将经分子对接后的34个优势构象组成训练集和11个优势构象组成测试集，构建三维定量构效关系(3D-QSAR)模型。COMFA模型的交叉验证系数(q2)，非交叉验证系数(R2)，标准偏差(SEE)和F值分别为0.761，0.973，0.122，185.963；自举法回归系数为R2bs=0.98。最佳组合COMSIA模型的q2，R2，SEE，F和R2bs分别为0.734，0.984，0.097，147.850，0.994。COMFA和COMSIA模型的系统外部测试R2pred分别为0.864和0.756， r2m分别为0.8127和0.5377。这些结果表明，所建立的QSAR模型具有较高的可靠性和较强预测能力。经三维等势图分析可知，在2、5或6位适当增加取代基体积，或在5位引入氢键受体，或在7位引入负电性取代基则能提高化合物的生物活性。该模型为进一步设计具有更优选择性和活性的化合物提供了理论依据。
醛酮還原酶1C3(AKR1C3)作為治療前列腺癌的新靶點已成為研究熱點，3-氨磺酰苯甲痠衍生物對其具有高效的選擇性和抑製活性。本文採用比較分子場分析(COMFA)和比較分子相似性指數分析(COMSIA)方法，將經分子對接後的34箇優勢構象組成訓練集和11箇優勢構象組成測試集，構建三維定量構效關繫(3D-QSAR)模型。COMFA模型的交扠驗證繫數(q2)，非交扠驗證繫數(R2)，標準偏差(SEE)和F值分彆為0.761，0.973，0.122，185.963；自舉法迴歸繫數為R2bs=0.98。最佳組閤COMSIA模型的q2，R2，SEE，F和R2bs分彆為0.734，0.984，0.097，147.850，0.994。COMFA和COMSIA模型的繫統外部測試R2pred分彆為0.864和0.756， r2m分彆為0.8127和0.5377。這些結果錶明，所建立的QSAR模型具有較高的可靠性和較彊預測能力。經三維等勢圖分析可知，在2、5或6位適噹增加取代基體積，或在5位引入氫鍵受體，或在7位引入負電性取代基則能提高化閤物的生物活性。該模型為進一步設計具有更優選擇性和活性的化閤物提供瞭理論依據。
철동환원매1C3(AKR1C3)작위치료전렬선암적신파점이성위연구열점，3-안광선분갑산연생물대기구유고효적선택성화억제활성。본문채용비교분자장분석(COMFA)화비교분자상사성지수분석(COMSIA)방법，장경분자대접후적34개우세구상조성훈련집화11개우세구상조성측시집，구건삼유정량구효관계(3D-QSAR)모형。COMFA모형적교차험증계수(q2)，비교차험증계수(R2)，표준편차(SEE)화F치분별위0.761，0.973，0.122，185.963；자거법회귀계수위R2bs=0.98。최가조합COMSIA모형적q2，R2，SEE，F화R2bs분별위0.734，0.984，0.097，147.850，0.994。COMFA화COMSIA모형적계통외부측시R2pred분별위0.864화0.756， r2m분별위0.8127화0.5377。저사결과표명，소건립적QSAR모형구유교고적가고성화교강예측능력。경삼유등세도분석가지，재2、5혹6위괄당증가취대기체적，혹재5위인입경건수체，혹재7위인입부전성취대기칙능제고화합물적생물활성。해모형위진일보설계구유경우선택성화활성적화합물제공료이론의거。
The human aldo-keto reductase family 1 member C3 (AKR1C3) has became a significant emerging target of therapeutic interest in prostate cancers. In the present work, 3D-QSAR model was established by a training set of 34 compounds and validated by the evaluation of a test set of 11 compounds, using the comparative molecular field analysis (COMFA) and comparative molecular similarity indices analysis (COMSIA) methods. Theq2,R2, SEE, F and theR2bs were 0.761, 0.973, 0.122, 185.963 and 0.98 respectively in COMFA model, and were 0.734, 0.984, 0.097, 147.850, and 0.994 respectively in optimum COMSIA model. The established 3D-QSAR model shows strong stability and good predictive ability. The systemic external validation parameters for COMFA and COMSIA models wereR2pred (0.864 and 0.756) andr2m (0.8137 and 0.5377), which validate the quality and predictive ability of 3D-QSAR model. Based on the 3D contour maps, if the volume of the substituent are increased appropriately at the 2, 5 or 6 positions of the template molecule, or hydrogen bond acceptor substituent was added to the 5 position of the template molecule, or the electronegative substituent was added to the 7 position of the template molecule, the biological activity of compounds will be improved. The generated models can provide useful information for designing new compounds with higher selectivity and stronger activity.
