In vitro activity of compounds isolated from Piper crassinervium against Trypanosoma cruzi

This study describes the antichagasic potential of five compounds isolated from leaves of Piper crassinervium (Piperaceae). Two prenylated benzoic acid derivatives, one prenylated hydroquinone and two flavanones, were evaluated. The in vitro trypanocidal activity was determined against epimastigote forms of Trypanosoma cruzi (Y strain), the etiologic agent of Chagas disease. The most active compound was the prenylated hydroquinone [1,4-dihydroxy-2-(3(0),7(0)-dimethyl-1(0)-oxo-2(0)-E,6(0)-octadienyl)benzene] with an IC(50) value of 6.10 microg mL(-1), which was in the same order of activity if compared with the positive control benznidazole (IC(50) = 1.60 microg mL(-1)). This is the first report of trypanocidal activity for prenylated hydroquinone and benzoic acid derivatives.     

Antimicrobial properties of volatile phenylpropanes

The examination of antimicrobial structure-activity relationships of 93 volatile phenylpropanes (VPs) and 21 related aromatic compounds revealed a dependence of antimicrobial activity from the kind and number of substituents on the aromatic ring, their substitution pattern and microbial characteristics, such as Gram coloring and strain specific factors. Eugenol isomers were predominantly inhibitory in a concentration range from 25 to 2000 mg/L against all microorganisms tested, which were three strains of Escherichia coli and Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, and Candida albicans. Etherified VPs were either less active or inactive depending on the type of side chain and/or substitution pattern. Differences in the antimicrobial activity of cis- and trans-isomers were observed. Species specific structure-activity relationships exist as was demonstrated with the Gram-negative bacteria (inactivity of E-ortho-eugenol) C. albicans (activity of di- and threefold methoxylated 1-propenylbenzenes), S. aureus and B. subtilis (activity of di-ortho methoxylated phenolic allylbenzenes and hydroquinone derivatives). With regard to the variety of observed specific effects and natural variation of susceptibility towards VPs according to literature reference data, the chances for successful prediction by computational analysis (QSAR) appear to be limited.     

Quantitative structure-activity relationships of H1-antihistaminic benzimidazole derivatives

The quantitative structure-activity relationships (QSAR) of 2-(4-substituted-1-piperazinyl)benzimidazole derivatives for antihistaminic activity were examined. Taking into consideration the specific conformations of some derivatives, a significant correlation was obtained using Verloop's STERIMOL parameters B3 and L of the substituent at the 1-position of the benzimidazole nucleus. The results indicated that the derivatives having a substituent with a small breadth and an appropriate length at the 1-position showed potent activity. From the results, a model of the binding site is proposed. The QSAR of side effects (anticholinergic activity and central nervous system depressive effect) were also examined and the results showed that a sterically small substituent at the 1-position was required to decrease side effects.     

酪氨酸蛋白激酶抑制剂:亚苄基丙二腈类衍生物定量构效关系的量子化学研究

用量子化学从头算方法,对亚苄丙二腈衍生物的定量构效关系(QSAR)进行了研究,结果显示:指示变量I,偶极矩Dipole和最低空轨道的能量ELUMO对亚苄丙二腈衍生物的抑制活性有很大影响,回归分析得到了相关性好的相关模型(R=0.95).I=0时,亚苄基丙二腈类衍生物的抑制作用由其化学反应性决定;I=1时其抑制作用由其静电性决定.     

Takaneones A-C, prenylated butylphloroglucinol derivatives from Hypericum sikokumontanum

Three new prenylated butylphloroglucinol derivatives, takaneones A-C (1-3), were isolated from the MeOH extracts of the aerial parts of Hypericum sikokumontanum together with two new prenylated phloroglucinol derivatives, takaneols A and B (4 and 5). The structures of the isolated compounds were elucidated by exhaustive spectroscopic analysis. The cytotoxicities of the isolated compounds against human cancer cell lines were evaluated. Compounds 2-4 showed cytotoxicities against K562/Adr multi-drug resistant (MDR) cancer cells with IC₅₀ values ranging from 4.7 to 10.0 μg/mL, which were slightly more potent than doxorubicin. Their potency of cytotoxicities against MDR cancer cell lines (KB-C2 and K562/Adr) were similar to those against sensitive cell lines (KB and K562).     

人工神经网络研究硝基苯化合物结构与毒性的关系

基于简单的化学基团描述符,应用人工神经网络研究了硝基苯类化合物对黑呆头鱼的毒性构效关系,并与多元线性回归相比较,结果显示了人工神经网络处理非线性问题的优越性.     

具有除草活性的大环内酯类衍生物的定量构效关系

研究了一系列结构新颖的具有除草活性的大环内酯衍生物的定量构效关系(QSAR). 构建的比较分子力场分析(CoMFA)、比较分子近似指数分析(CoMSIA)和全息定量构效关系(HQSAR)分子模型的交叉验证系数r2cv均大于0.5, 非交叉验证系数r2都超过0.8, 表明获取的QSAR模型具有可信的预测能力. 对CoMFA、CoMSIA模型的三维(3D)等势图分析, 发现除了立体场和静电场外, 疏水场和氢键受体场也是影响大环内酯类化合物除草活性的重要因素. 构建的HQSAR模型的原子贡献图提示的结构改造信息与三维QSAR的结果基本一致. 利用CoMFA、CoMSIA模型提供的信息,对目前已合成的活性最高化合物B1-3进行分子结构改造, 预测结果发现部分化合物可能具有更好的除草活性.     

Nonlinear dependence in comparative molecular field analysis

Summary The applicability of the comparative molecular field analysis (CoMFA) approach to describe the nonlinear dependence of biological activity on lipophilicity in 3D quantitative structure-activity relationships (QSAR) has been demonstrated. The results indicate that the CoMFA approach is appropriate for describing nonlinear effects in 3D QSAR studies.     

2-氯苯甲酰基苯基脲系列化合物对昆虫几丁质的抑制作用

本文用二令淡色库蚊(Culex Pipiens Pallens)对2-氯苯甲酰基苯基脲及其硫脲进行定量构效关系的研究,找出合成高效无氟昆虫几丁质抑制剂的结构因素。     

Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin

Chemical investigation of the marine sponge Plakortis cfr. lita afforded a library of endoperoxyketal polyketides, manadoperoxides B-K (3-5 and 7-13) and peroxyplakoric esters B(3) (6) and C (14). Eight of these metabolites are new compounds and some contain an unprecedented chlorine-bearing THF-type ring in the side chain. The library of endoperoxide derivatives was evaluated for in vitro activity against Trypanosoma brucei rhodesiense and Leishmania donovani. Some compounds, such as manadoperoxide B, exhibited ultrapotent trypanocidal activity (IC(50) = 3 ng mL(-1)) without cytotoxicity. Detailed examination of the antitrypanosomal activity data and comparison with those available in the literature for related dioxane derivatives enabled us to draw a series of structure-activity relationships. Interestingly, it appears that minor structural changes, such as a shift of the methyl group around the dioxane ring, can dramatically affect the antitrypanosomal activity. This information can be valuable to guide the design of optimized antitrypanosomal agents based on the dioxane scaffold.