<p>Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches</p>

Abstract

Background: Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature. Materials and Methods: In the current study, we synthesized a series of water-soluble fullerene derivatives and observed their anti-tumor effects on human lung carcinoma A549 cell lines. The quantitative structure-activity relationship (QSAR) modeling was employed to investigate the relationship between anticancer effects and descriptors relevant to peculiarities of molecular structures of fullerene derivatives. Results: In the QSAR regression model, the evaluation results revealed that the determination coefficient r 2 and leave-one-out cross-validation q 2 for the recommended QSAR model were 0.9966 and 0.9246, respectively, indicating the reliability of the results. The molecular modeling showed that the lack of chlorine atom and a lower number of aliphatic single bonds in saturated hydrocarbon chains may be positively correlated with the lung cancer cytotoxicity of fullerene derivatives. Synthesized water-soluble fullerene derivatives have potential functional groups to inhibit the proliferation of lung cancer cells. Conclusion: The guidelines obtained from the QSAR model might strongly facilitate the rational design of potential fullerene-based drug candidates for lung cancer therapy in the future.

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

“…Chemical structures of twenty water-soluble fullerene derivatives 1 – 20 [54] and the survival rates for A549, H460, and H1299 NSCLC lung cancer cells treated with the aforementioned compounds are listed in Table 1 . The standard deviation (SD) of each survival rate was measured from three independent experimental groups via MTT assay.…”

“…In order to build a more reasonable QSAR model, we included the experimental data of ten fullerene derivatives from our previous report and then combined with data from the current study for model constructions. Because the ten fullerene derivatives synthesized in our previous literature only had bio-activity data for A549 cells [54] , the survival rate of the H460 and H1299 cells were evaluated in the current study after treatment by the ten fullerene compounds in the concentration of 400 μM ( Fig. 2 ).…”

“…We further analyzed the descriptors suggested from the three different recommended equation models responsible for the individual survival rate of A549, H460, and H1299. Regarding the linear regression model of A549 cells from our previous work [54] , the suggested molecular descriptors were S_Count , ES_Count_dO , ES_Count_sCl , AliphaticSingleBounds , AromaticRings , H_Acceptors , and RingBonds . Comparing two equation models from previous and current studies on A549, we noted that the key features including oxygen atom and chlorine atom are given by both equations.…”

“…The recommended equation model of H1299 had two critical molecular descriptors that has been displayed in a previously reported equation model of A549 [54] , including ES_Count_sCl , and Num_AliphaticSingleBonds descriptors. Our previous study demonstrated that lower numbers of chlorine atoms and aliphatic single bonds on the soluble addends of fullerene compounds promoted the antitumor activities on A549 cells.…”

“…Spectral data for compounds 8 – 10 have been published earlier [53] . Compounds 11 – 20 have been obtained and characterized as reported previously by our group [54] .…”