Influence of LC Retention Data on Antitumor Acridinones’ Classification Evaluated by Factor Analysis Method

Marcin      Koba; Tomasz      Baczek; Tomasz      Ciesielski

doi:10.2174/138620712802650531

Abstract

The application of factor analysis (FA) method in classification of the antitumor acridinones based on highperformance liquid chromatography (HPLC) retention data and calculated parameters of lipophilicity as well as some nonempirical structural parameters was studied. First, a group of 19 acridinone (imidazoacridinone and triazoloacridinone) derivatives was chromatographed in six RP-HPLC systems, and the values of their HPLC retention data as retention’ times determined in both 10 min and 30 min gradient times were obtained as well as log kw (retention factor log k extrapolated to 0% organic modifier) parameters using DryLab program were calculated. Additionally, molecular modeling studies were performed based on the structural formula of considered acridinones and structural descriptors were derived as well as log P parameters using some commonly available software were calculated and subsequently used. A matrix of 19 x 32 HPLC data together with log P data and molecular properties parameters was subjected to factor analysis and led to extract three main factors with eigenvalues higher than 1. The first principal component (factor 1) accounted for, by 80.87% of the variance in data, the second principal component (factor 2) explained 7.77% and the third principal component (factor 3) was responsible by 4.46% of data variance. The total data variance was at the level 93.09% and was explained by the first three principal components. Moreover, one of the most significant influences on the values of factor 1 and factor 2 possessed HPLC retention data and calculated parameters describing lipophilicity, respectively. More importantly, distribution of individual drugs on the plane determined by two principal components produced patterns in good agreement with their chemical structures as well as with their antitumor activity.

Keywords: Acridinones, factor analysis (FA), gradient reversed-phase high-performance liquid chromatography (RP-HPLC), lipophilicity, pharmacological classification, Antitumor Activity acridinones, triazoloacridinones, imidazoacridinones, drug design, anticancer activities