Multivariate SAR and QSAR of cucurbitacin derivatives as cytotoxic compounds in a human lung adenocarcinoma cell line

LANG K. L.; SILVA I.T.; MACHADO V. R.; ZIMMERMANN L. A.; CARO M. S. B.; SIMOES C. M. O.; SCHENKEL E. P.; DURAN F. J.; BERNARDES L. S. C.; BORGES DE MELO E.

JOURNAL OF MOLECULAR GRAPHICS & MODELLING.

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2014 vol. 48 p. 70 - 79

1093-3263

This article describes structure-activity relationship (SAR/QSAR) studies on the cytotoxic activity in a human lung adenocarcinoma cell line (A549) of 43 cucurbitacin derivatives. Modeling was performed using regression by partial least squares with discriminant analysis (PLS-DA) and by the PLS calibration method. For both studies, the variables were selected using the ordered predictor selection (OPS) algorithm. The SAR study demonstrated that the presence or absence of cytotoxic activity of the cucurbitacins could be described using information derived from their chemical structures. The model obtained in the QSAR study displayed suitable internal and external predictivity. Furthermore, the selected descriptors indicated that the observed activity might be related to electrophilic attack on cellular structures or genetic material. This study provides improves the understanding of the cytotoxic activity of cucurbitacins and could be used to propose new cytotoxic agents.