Role of Weak Molecular Interactions in the Mechanism of Action of a Series of Antihelmintics 英文参考文献.docVIP

317 Molecules 2000, 5 Role of Weak Molecular Interactions in the Mechanism of Action of a Series of Antihelmintics Marisa Santo1, Liliana Giacomelli1, Mario Reta1, Rosa Cattana1, Juana Silber1, Antonio Chana2, Mercedes Rodriguez2 and Carmen Ochoa2 1Departamento de Química y Física. Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Uni- versidad Nacional de Río Cuarto, Agencia Postal No 3 (5800) Río Cuarto, Argentina 2Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Espa?a Abstract: Different physicochemical properties such as solute-solute and solute-solvent in- teractions, tautomerism, lipophilicity and solubility in water were determined for a serie of 6,7-diaryl-pteridines in order to relate those properties with their nematocide action. Introduction The pharmacological response of a drug can be the result of a complex formation between the drug and the receptor. This complex is generally the result of several types of interactions such as hydro- phobic and electrostatic forces, hydrogen bonding and electron donor-acceptor complexes [1]. Previous works [2,3] have shown the nematocide activity for a serie of substituted 6,7-diaryl- pteridines (I) against different experimental models. Different structure-activity relationships (SARs) have been established for these compounds through neural networks [3]. 4 5 N Ar 3 N 6 7 Ar 2 I N N 1 8 Experimental Synthesis and nematocide accion for the studied compounds were previously described [2,3]. Results and Discussion For 18 substituted 6,7-diaryl-pteridines the following physicochemical properties were determined: polar and hydrogen bonding interactions with the solvent, solute-solute interactions, tautomerism,  318 Molecules 2000, 5 solubility in water and lipophilicity. It was observed that only lipophilic interactions are related with the measured nematocide action (%R) for these drugs.