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The Synergistic Cytotoxic Effect of the Two Enantiomers of 6-Prenylflavanones in the HeLa Cell Line

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide This research performed a structure–activity relationship (SAR) study, which involved the synthesis of 16 ( 2R/S )-6-PFVNs and evaluating their cytotoxic effects on the HeLa cell line. This investigation concentrated on the length of the prenyl side chain at the C-6 position of the A-ring and the substitution patterns of the methoxy and hydroxy groups on the B-ring. Accordingly, several ( 2R/S )-6-PFVNs were identified as having strong cytotoxic effects on HeLa cells. Among them, ( 2R/S )-6-(3,3-diethylallyl)naringenin (6-DEANG) emerged as a standout candidate, demonstrating an IC 50 value of 12 μM and a selectivity index (SI) exceeding 10. Furthermore, the synergistic effect of ( 2R )-6-DEANG and ( 2S )-6-DEANG on the treatment of HeLa cells with ( 2R/S )-6-DEANG was determined by comparing the IC 50 value of ( 2R/S )-6-DEANG to those of the individual enantiomers, which were isolated through chiral chromatography. This synergistic effect was further confirmed through the median-effect plot and the combination index versus the fraction of affected cells (CI-Fa) plot. Additionally, molecular docking studies revealed that ( 2S )-6-DEANG had a higher affinity for various proteins, while ( 2R )-DEANG demonstrated stronger binding to other proteins. A similar effect of ( 2S )-KTt-45 and ( 2R )-KTt-45 was also observed. Overall, the findings of this study clearly highlight the potential of ( 2R/S )-6-PFVNs as effective agents in the treatment of cervical cancer.

Source: ACS Omega

DOI: 10.1021/acsomega.5c02553