Exploring Structure-Activity Relationships for the In vitro Cytotoxicity of Alkylphenols (APs) toward HeLa Cell

In vitro cytotoxicity of 23 alkylphenols (APs) on human cervical cancer cell lines (HeLa) was determined using the lactate dehydrogenase (LDH) cytotoxicity assay. Two different sets of descriptors were used to construct the calibration model based on Genetic Algorithm-Multiple Linear Regression (GA-MLR) based on the experimental data. A statistically robust Structure-Activity Relationships (QSAR) model was achieved (R-2=95.05%, Q(LOO)(2)=91.23%, F=72.02 and SE= 0.046) using three Dragon descriptors based on Me (OD-Constitutional descriptor), BELp8 (2D-Burden eigenvalue descriptor) and HIATS8p (3D-GETAWAY descriptor). However, external validation could not fully prove its validity of the selected QSAR in characterization of the cytotoxicity of APs towards HeLa cells. Nevertheless, the cytotoxicity profiles showed a finding that 4-n-octylphenol (4-NOP), 4-tert-octylphenol (4-TOP), 4-n-nonylphenol (4-NNP) had a more potent cytotoxic effect than other APs tested, inferring that increased length and molecular bulkiness of the substituent had important influence on the LDH cytotoxicity.