Abstract

ANALYSIS OF THE CYTOTOXICITY OF SOME DIHYDROPHENANTHRIDINE-1, 7, 10(4H)-TRIONES AGAINST SK-MES-1D HUMAN LUNG CANCER CELL LINE VIA MOLECULAR MODELING

Mohamed Osman M. A. El-Fakii*, Maeen Ahmed M. A. AL-Mansori and Enas Osman Khojali

ABSTRACT

The variability of anticancer activity of a set of 24 known Phenanthridine-1, 7, 10(4H)-triones Was followed by regressing biological response against lipophilicity, combined steric/polarizability effect and steric bulk. The biological response is represented by the inhibitory concentration (IC50) against human Lung Cancer (SK-MES-1d) cell line. Lipophilicity is represented by the logarithm of octanol/water partition coefficient (Log P), the combined steric/polarizability effects is represented by molar refractivity (MR) and the steric bulk is represented by molar volume (MV). On running regression analysis, the physicochemical parameters and (IC50) show very weak correlations as evident by the low values of statistical correlation coefficient R2 (0.1 to 0.2). As each compound shows significant activity (in the range of 1 to 96 M), clustering was used to uncover mechanistic hidden subgroups inside the main data sets. This was done by a type of clustered regression analysis previously described. The clustering was based on correlating each of parameter with the response and the outcomes were scrutinized for the parameter which give the best clustering. Thus, MR was chosen as it gave five clusters with high R2 values (ranging from 0.99 to 0.88). The other two parameters (log P and MV) were clustered according to MR-based clustering to give in depth support to our clustering approach

Keywords: dihydrophenanthridinetriones DPT, QSAR, clustering, mechanistic profile.