Journal of Physical Chemistry & Biophysics
Open Access

Abstract

Binding Affinities and Cytotoxicity of Novel Psoralen Derivatives: A Fluorescence Spectroscopy Study

Cameron M. Puhl and Francis P. Gasparro*

Psoralens are naturally occurring compounds used in clinical settings to treat skin diseases and cancers. Their therapeutic efficacy stems from their ability to intercalate between DNA base pairs, and once activated by ultraviolet A (UVA) light, form mono- and di-adducts that initiate apoptosis. Although a few psoralen derivatives (like 8-MOP, TMP, and AMT) are widely used in treatments such as PUVA (psoralen plus ultraviolet A) and X-PACT (X-Ray Psoralen Activated Cancer Therapy), many other psoralen derivatives with unique structures have not yet been studied. In the present study, we investigated the binding affinities of three novel psoralen derivatives (1B, 6D, and 2F) with a synthetic adenine-thymine polynucleotide (AT-40) using fluorescence spectroscopy. We analyzed the fluorescence quenching data with Scatchard plots to determine the relative binding constants, and then compared those values to previously reported cytotoxicity data. Results showed that 2F exhibited the greatest binding constant (3.43 × 10⁶ M^-1), followed by 6D and 1B, indicating that certain structural features such as protonated substituents and side chain position may impact DNA intercalation. Additionally, comparisons between binding strength and cell survival after UVA exposure revealed a moderate inverse correlation, suggesting that stronger DNA binding may increase cytotoxicity. In particular, 2F appeared to have therapeutic potential because of its high binding constant and cytotoxicity. These findings highlight the significance of psoralen structure in binding and cytotoxic effectiveness and call for further in vivo studies of derivatives with high binding affinity like 2F.

Published Date: 2025-10-03; Received Date: 2025-08-26