Development and interpretation of a QSAR model for in vitro breast cancer (MCF-7) cytotoxicity of 2-phenylacrylonitriles.

Stanton, David T.; Baker, Jennifer R.; McCluskey, Adam; Paula, Stefan

The Arylhydrocarbon Receptor (AhR), a member of the Per-ARNT-SIM transcription factor family, has been as a potential new target to treat breast cancer sufferers. A series of 2-phenylacrylonitriles targeting AhR has been developed that have shown promising and selective activity against cancerous cell lines while sparing normal non-cancerous cells. A quantitative structure–activity relationship (QSAR) modeling approach was pursued in order to generate a predictive model for cytotoxicity to support ongoing synthetic activities and provide important structure-activity information for new structure design. Recent work conducted by us has identified a number of compounds that exhibited false positive cytotoxicity values in the standard MTT assay. This work describes a good quality model that not only predicts the activity of compounds in the MCF-7 breast cancer cell line, but was also able to identify structures that subsequently gave false positive values in the MTT assay by identifying compounds with aberrant biological behavior. This work not only allows the design of future breast cancer cytotoxic activity in vitro, but allows the avoidance of the synthesis of those compounds anticipated to result in anomalous cytotoxic behavior, greatly enhancing the design of such compounds.

BREAST cancer; QSAR models; STRUCTURE-activity relationships; CELL lines; TRANSCRIPTION factors; CHALCONE

Journal of Computer-Aided Molecular Design, 2021, Vol 35, Issue 5, p613

0920-654X

Academic Journal

10.1007/s10822-021-00387-5