Identification of potential descriptors of water-soluble fullerene derivatives responsible for antitumor effects on lung cancer cells via QSAR analysis

Water-soluble fullerene derivatives are actively investigated as potential drugs for cancer treatment due to their favorable membranotropic properties. Herein, cytotoxic effects of twenty fullerene derivatives with different solubilizing addends were evaluated in three different types of non-small-cell lung carcinoma (NSCLC). The potential structural descriptors of the solubilizing addends related to the inhibitory activities on each type of lung cancer cell were investigated by the quantitative structure–activity relationship (QSAR) approach. The determination coefficient r(2) for the recommended QSAR model were 0.9325, 0.8404, and 0.9011 for A549, H460, and H1299 cell lines, respectively. The results revealed that the chemical features of the fullerene-based compounds including aromatic bonds, sulfur-containing aromatic rings, and oxygen atoms are favored properties and promote the inhibitory effects on H460 and H1299 cells. Particularly, thiophene moiety is the key functional group, which was positively correlated with strong inhibitory effects on the three types of lung cancer cells. The useful information obtained from our regression models may lead to the design of more efficient inhibitors of the three types of NSCLC.