大黄素衍生物抗肿瘤活性的定量构效关系

目的 建立大黄素衍生物抗肿瘤活性的构效关系模型.方法 采用量子化学的AM1算法计算了12个大黄素衍生物的分子结构参数,利用逐步回归分析建立构效关系模型.结果 成功建立了大黄素衍生物抗肿瘤活性的构效关系模型.结论 大黄素衍生物抗肿瘤活性与分子体积V、极化率α及C环上净电荷QC相关.     

吡咯烷类明胶酶抑制剂的合成及初步活性

目的设计合成一系列新型吡咯烷衍生物并测定其抑制明胶酶（MMP-2，MMP-9）的活性，研究其构效关系。方法以L-羟脯氨酸为原料。经多步反应合成吡咯烷类衍生物，采用体外抑酶试验测定化合物抑制明胶酶（MMP-2，MMP-9）的活性。结果合成了33个未见文献报道的吡咯烷衍生物，其结构经红外光谱、核磁共振氢谱及质谱确定。其中化合物A0、A8、A9、A10、B9、C10抑制明胶酶的活性较强。结论吡咯烷类衍生物对明胶酶有较强的抑制活性。有可能抑制肿瘤的发生、发展和转移，值得进一步研究。     

Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu(II) ions: mechanism and structure-activity relationship.

The prooxidant effect of hydroxycinnamic acids (HCAs), i.e., caffeic acid (CaA), chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA), 3-hydroxycinnamic acid (3-HCA) and 4-hydroxycinnamic acid (4-HCA) on supercoiled pBR322 plasmid DNA strand breakage and calf thymus DNA damage in the presence of Cu(II) ions has been studied. It was found that the compounds bearing ortho-dihydroxyl group (CaA and ChA) or bearing 4-hydroxy-3-methoxyl group (SA and FA) exhibited remarkably higher activity in the DNA damage than the ones bearing no such functionalities. The good correlation between the DNA damaging activity and the oxidative potential of the compounds indicates that the electron transfer between HCAs and Cu(II) plays a crucial role in the reaction. UV-Visible spectral changes demonstrated that CaA or ChA can chelate with Cu(II) as a bidentate ligand, hence facilitating intramolecular electron transfer between CaA or ChA and Cu(II). The involvement of reactive oxygen species (ROS) and Cu(I) ions in the DNA damage were affirmed by the inhibition of DNA breakage using mannitol, glutathione (GSH), catalase and bathocuproinedisulfonic acid (BCDS). These results may have important implications regarding the proposed mechanism of apoptosis induced by phenol and endogenous metal ions.     

以基团为基准借电负性修正的分子距边矢量对N，N-二甲基-2-溴苯乙胺类衍生物进行结构表征和活性预测

以基团为基准并借助电负性修正分子距边矢量 (VMDE) ,对N ,N 二甲基 2 溴苯乙胺类衍生物的结构进行表征 ,然后用多元线性回归技术 (MLR)建立新分子距边矢量与其生物活性的相关关系 ,结果表明 :新分子距边矢量与生物活性之间有良好的线性关系 ,复相关系数高达R =0 96 75 ,均方根误差RMS =0 140 ,解释方差EV =0 96 19,统计量F =87 8,优于文献使用常规取代基参数获得的结果 :R =0 917,S =0 2 38,F =5 0 1.为检查模型的稳定性和预测能力 ,还作了随机抽样检验和交互校验 ,结果优良     

In vitro structure-activity relationship and in vivo studies for a novel class of cyclooxygenase-2 inhibitors: 5-aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives

5-Aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives were studied as a novel class of selective cyclooxygenase-2 inhibitors with regard to synthesis, in vitro SAR, antiinflammatory activities, pharmacokinetic considerations, and gastric safety. 1f, a representative compound for methyl sulfone derivatives, showed a COX-2 IC(50) comparable to that of rofecoxib. In case of 20b, a representative compound for sulfonamide derivatives, a potent antiinflammatory ED(50) of 0.1 mg kg(-1) day(-1) was observed against adjuvant-induced arthritis by a preventive model, positioning 20b as one of the most potent COX-2 inhibitors ever reported. Furthermore, 20b showed strong analgesic activity as indicated by its ED(50) of 0.25 mg/kg against carrageenan-induced thermal hyperalgesia in the Sprague-Dawley rat. 3(2H)Furanone derivatives showed due gastric safety profiles as selective COX-2 inhibitors upon 7-day repeat dosing. A highly potent COX-2 inhibitor of the 3(2H)furanone scaffold could be considered suitable for a future generation COX-2 selective arthritis medication with improved safety profiles.     

Synthesis and antimicrobial activity of 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl) propyl)piperidine derivatives against pathogens of <Emphasis Type="Italic">Lycopersicon esculentum</Emphasis>: A structure-activity evaluation study

Several 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl)propyl)piperidine derivatives 8(a–j) were prepared by the treatment of substituted benzhydryl chlorides with 4-(3-(piperidin-4-yl)propyl)piperidine followed by N-sulfonation with sulfonyl chlorides in the presence of dry methylene dichloride and triethyl amine. The synthesized compounds were characterized by ¹H-NMR, IR, and elemental analysis. All the synthesized compounds were evaluated in vitro for their efficacy as antimicrobial agents by artificial inoculation technique against standard strains of two important bacterial viz., Xanthomonas axonopodis pv. vesicatoria and Ralstonia solanacearum as well as and two fungal pathogens namely Alternaria solani and Fusarium solani of tomato plants. We have briefly investigated the structure-activity relation studies and reveal that the nature of substitutions on benzhydryl ring and sulfonamide ring influences the antibacterial activity. Among the synthesized new compounds 8b, 8d, 8g, 8h, 8i, and 8j were showed significant potent antimicrobial activities compared to the standard drugs Chloramphenicol, Mancozeb.     

Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals

Most exposure levels of flavor in food are considered to be extremely low. If at all, genotoxic properties should be taken into account in safety evaluations. We have recently established a (quantitative) structure–activity relationship, (Q)SAR, combination system, which is composed of three individual models of mutagenicity prediction for industrial chemicals. A decision on mutagenicity is defined as the combination of predictive results from the three models. To validate the utility of our (Q)SAR system for flavor evaluation, we assessed 367 flavor chemicals that had been evaluated mainly by JECFA and for which Ames test results were available. When two or more models gave a positive evaluation, the sensitivity was low (19.4%). In contrast, when one or more models gave a positive evaluation, the sensitivity increased to 47.2%. The contribution of this increased sensitivity was mainly due to the result of the prediction by Derek for Windows, which is a knowledge-based model. Structural analysis of false negatives indicated some common sub-structures. The approach of improving sub-structural alerts could effectively contribute to increasing the predictability of the mutagenicity of flavors, because many flavors possess categorically similar functional sub-structures or are composed of a series of derivatives.