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A methanolic extract and two fractions (n-hexane and ethyl acetate) from Virola oleifera leaves and some compounds (one lignan and two flavonoids) were investigated to verify the analgesic activity by using the writhing test in mice. The crude methanolic extract showed a moderate analgesic effect (about 40% of inhibition in this test at 10 mg/kg), whereas n-hexane and ethyl acetate fractions caused inhibition of 51.3 ± 5.9% and 50.5 ± 6.3% , respectively. Oleiferin-C (1), a lignan isolated from the n-hexane fraction, showed an interesting analgesic potential in this model when compared to two standard drugs, paracetamol (4-acetamidophenol) and aspirin (acetylsalicylic acid). The ID50 calculated for this compound was 17.25 μmol/kg, with confidence interval between 13.7 and 21.3 μmol/kg, being about 8 times more potent than the standard drugs. The mixture of two glycoside-flavonoids, identified as astilbin (2) and quercitrin (3), also exhibited good analgesic activity, causing 63% of reduction of abdominal constriction in mice. These results suggest beneficial effect of this plant to treat dolorous processes.

Quantitative structure-activity relationships (QSAR) were used in this study to relate the structural parameters (electronic, topological, etc.) to the odor of 27 aliphatic esters previously evaluated by Rossiter. Rossiter used the Hansch approach, principal component analysis and comparative molecular field analysis (CoMFA) to predict the odor of these esters. Different structural parameters were selected, such as topological, physicochemical, and quantum-chemical indices, to find an equation to predict the molecular factors that determine the fruit odor of these compounds and to compare such results with those obtained by Rossiter. Two significant correlation equations were obtained with the following molecular descriptors: one with the electrotopological-state index related to the carbon atom of the carbonyl group (S(C)(=)(O)), the Kappa index ((2)Kappa), and the topological-state index related to the oxygen on the alcoholic side of the molecule (T(-)(O)(-)), and the other with (2)Kappa, S(C)(=)(O), and the energy of the highest occupied molecular orbital (E(HOMO)). The model found had a good predictive ability as established by cross-validation r(2)(cv) values and thus can be used to help in the prediction of odor of similar compounds. This method is simplier than the methods used by Rossiter and represents a reliable QSAR alternative in predicting the fruit odor of such aliphatic esters.

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The optimization of the properties of a lead compound is the first goal of most pre-clinical research projects. Optimization strategies may be applied to the synthesis of analogous compounds in order to minimize cost and time. One strategy of synthesis is the change of the substituents in the molecule. The manual method of Topliss was introduced for the prediction of the substituted compounds that will have the most potent activity in a series of aromatic substituted analogues.A modified Topliss method is proposed that consist of the quantitative correlation by a single regression equation ZusammenfassungVon der manuellen Topliss-Methode hin zu einer modifizierten quantitativen Methode Die Optimierung der Eigenschaften einer Leitsubstanz ist das vorrangige Ziel der meisten vorklinischen Forschungsprojekte. So können Optimierungsstrategien für die Synthese von Analogsubstanzen angewendet werden, um Kosten und Zeit zu minimieren. Eine Strategie in diesem Sinne ist der Austausch von Substituenten in den Molekülen. Die Methode nach Topliss wurde für die Voraussage von substituierten Produkten eingeführt, wobei die höchste Aktivität in einer Serie von aromatischen substituierten Verbindungen auftritt.Es wird eine modifizierte Topliss-Methode vorgestellt, bei der quantitative of the activity of a series of 4 or 5 substituted aromatic compounds with the descriptor parameters: hydrophobic (π), electronic (σ) and sterics (Es and MR) and some combinations of them in order to predict future synthesis, or to obtain a training set of compounds to be used in the application of more advanced experimental design methods. These results when compared with those of multiple regression analysis applying the Hansch equation are very satisfactory. Korrelationen durch einfache Regressionen von Aktivitäten in einer Serie von 4-oder 5-susbstituierten aromatischen Verbindungen mit folgenden Beschreibungsparametern möglich sind: hydrophobisch (π), elektronisch (σ) und sterisch (Es und MR) und einige Kombinationen davon, um zukünftige Synthesen voraussagen zu können oder um Leitsubstanzen zu erhalten, die in fortgeschritteneren experimentellen Design-Methoden weiterverwendet werden können. Die folgende Ergebnisse sind, verglichen mit denen der multiplen Regressionsanalyse unter Verwendung der Hansch-Methode, sehr zufriedenstellend. Key words Drug design Quantitative structureactivity relationship Structure-activity relationship Topliss method, modified Arzneim.-Forsch./Drug Res. 52, No. 2, 125−132 (2002) Arzneim.-Forsch./Drug Res. 52, No. 2, 125−132 (2002) Yunes et al. − Modified Topliss method 125