Retrospective Benchmarking of Previously Modeled Coumarin–Pyrimidine Structures Against MDA-MB-231/MCF-10A Cellular Activity

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Abstract
This study retrospectively evaluates agreement between target-level molecular-modeling rankings from a previously published coumarin–pyrimidine library and an available cellular dataset for 14 experimentally evaluated compounds with documented structure assignments. Laboratory-reported MDA-MB-231 and MCF-10A IC50 values from multi-concentration MTT testing were compared with published AutoDock Vina scores using rank-based analyses. Compound 5e had the lowest laboratory-reported MDA-MB-231 IC50 (12.4 ± 0.2 µM; n = 2) and the largest descriptive selectivity index (7.75); this ratio is specific to the MDA-MB-231/MCF-10A comparison and is not interpreted as evidence of general tumor selectivity. Docking rankings showed weak correspondence with cellular potency, and no docking–phenotype association remained statistically significant after Benjamini–Hochberg adjustment. No basic 2D descriptor showed a compelling adjusted association. Complete 1H/13C NMR and validated HRMS documentation, quantitative purity measurements, and the complete full-series MTT raw export are not available; structure-dependent and potency claims are therefore interpreted cautiously. Overall, the analysis demonstrates limited cross-endpoint transferability between target-level docking rankings and whole-cell activity in the MDA-MB-231/MCF-10A dataset, without establishing a validated structure–activity relationship, generalized TNBC activity, apoptosis induction, a BCL-2 mechanism, or translational efficacy.

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