From Hansch‐Fujita Analysis to AFMoC: A Road to Structure‐Based QSAR

Abstract

Since the pioneering effort of Hansch and Fujita, quantitative structure-activity relationships (QSAR) have proved valuable in optimizing lead structures. Enriching classical 3D-QSAR analysis, which exploits the three-dimensional structure of ligands, with structural information of the target has helped to improve the interpretability of the derived models and to increase their predictive power. One such method is the Adaption of Fields for Molecular Comparison (AFMoC) approach where protein-specifically adapted knowledge-based pair-potentials are tailored to one particular protein by considering additional structural and energetic information about ligands. Here, we summarize applications of AFMoC, describe recent developments, and provide an outlook on how to improve the method.

Synthesis, Theoretical Study, and Anticonvulsant Evaluation of N‐Arylenaminones

“…The quantitative structure‐activity relationship analysis (QSAR) was performed under the QSAR‐2D model proposed by Hansch and Fujita [69–71] …”

“…The quantitative structure-activity relationship analysis (QSAR) was performed under the QSAR-2D model proposed by Hansch and Fujita. [69][70][71] Concerning the physicochemical properties of the N-arylenaminones, the lipophilicity was estimated through the partition coefficient (logP), [72,73] this parameter was determined on CS ChemDraw Pro v.6 software and ACD/ChemSketch 2015. [74,75] The estimation of the π values was carried out by means of the following equation:…”

Physicochemical Interpretation, with QSAR/SAR Analysis, of How the Barriers Of Pseudomonas Aeruginosa Bacteria Were Penetrated by Para-Substituted N-Arylbenzylimines: Synthesis, Characterization, and In Vitro Antibacterial Effect

“…The QSAR was performed under QSAR-2D, proposed by Corwin Hansch and Toshio Fujita [49,50]. Concerning the physicochemical properties of the N-arylbenzylimines, size was measured by molar refractivity (Advanced Chemistry Development, Inc.) and lipophilicity by the partition coefficient [51,52].…”

Aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade de brometos de amônio quaternários estruturalmente análogos a procaína, com atividade de bloqueio da transmissão neuromuscular, para estudos de <i>(Q)SAR</i>

“…O modelo matemático original, proposto por Hansch e Fujita, que relaciona a atividade/resposta biológica de uma série de compostos com seus parâmetros físico-químicos/estruturais, pode ser representado pela seguinte equação (Hansch & Fujita, 1964): Para se estabelecer relações entre os parâmetros físico-químicos/estruturais e a atividade biológica utilizando esta abordagem, deve-se utilizar uma série congênere de compostos, ou seja, devem apresentar uma estrutura fundamental e, além disso, exercer a atividade/resposta biológica pelo mesmo mecanismo de ação (Kubinyi, 1993;Siqueira, 2001;Gertzen & Gohlke, 2012 (Kubinyi, 1993;Tropsha & Golbraikh, 2007;Alexander et al, 2015).…”

“…Esta abordagem, embora seja bastante eficaz neste sentido, apresenta limitação em relação à abordagem do aspecto tridimensional das relações ligante-receptor (Kubinyi, 1993;Rusyn et al, 2012;Cherkasov, 2014 (Kubinyi, 1993;Pires et al, 2001;Ishiki & Amaral, 2009;Doweyko, 2004;Malvezzi et al, 2009;Gertzen & Gohlke, 2012;Sliwoski et al, 2016).…”