QSAR on antiproliferative naphthoquinones based on a conformation-independent approach

• A set of 1,2-furanonaphthoquinones with a hydroxyl group at aromatic ring were synthesized.
• The Antiproliferative activities of 36 naphthoquinones were subjected to a QSAR study.
• A conformation-independent representation of the chemical structure was established.
• The established linear models were specific to the each cancer cell line.
• The established models were validated and tested through the use of external test sets of compounds.

The antiproliferative activities of a series of 36 naphthoquinone derivatives were subjected to a Quantitative Structure–Activity Relationships (QSAR) study. For this purpose a panel of four human cancer cell lines was used, namely HBL-100 (breast), HeLa (cervix), SW-1573 (non-small cell lung) and WiDr (colon). A conformation-independent representation of the chemical structure was established in order to avoid leading with the scarce experimental information on X-ray crystal structure of the drug interaction. The 1179 theoretical descriptors derived with E-Dragon and Recon software were simultaneously analyzed through linear regression models based on the Replacement Method variable subset selection technique. The established models were validated and tested through the use of external test sets of compounds, the Leave-One-Out Cross Validation method, Y-Randomization and Applicability Domain analysis.

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