A Quantum-Chemical Study of the In vitro Cytotoxicity of a Series of (Z)-1-Aryl-3-Arylamino-2-Propen-1-Ones Against Human Tumor DU145 and K562 Cell Lines

In this paper we present the results of a formal quantum-chemical analysis of the relationships between the electronic structure and In vitro cytotoxicity activity (measured in a cell-based assay using two different human tumor cell lines derived from human prostate cancer and leukemia) for a series of (Z)-1-aryl-3-arylamino-2-propen-1-ones. We employed a formal method relating biological activities with local atomic reactivity indices developed in our Unit. The electronic structure of all molecules was calculated within Density Functional Theory at the B3LYP/6-31g (d,p) level of theory with full geometry optimization. We have obtained statistically significant results relating the variation of a definite set of local atomic reactivity indices to the variation of toxicity against the DU-145 cell line. No local atomic reactivity indices belonging to the chain joining the phenyl rings appear in the final equation. Therefore it is not possible to elaborate about its role. Phenyl rings seem to play opposite roles regarding electron transfer. The whole process is charge-, orbital- and sterically-controlled. No good results were obtained for the K562 cell line. More experimental information is needed to clarify this last result.