Novel psoralen derivatives as anti-breast cancer agents and their light-activated cytotoxicity against HER2 positive breast cancer cells

• DOI: 10.1038/s41598-022-17625-x
• Publication Date: 2022-08-05T13:05:45Z
• Authors: Chiphada Aekrungr...; Sirilak Wangngae; Anyanee Kamkaew; Ruchuta Ardkhean; Sanit Thongnest; Jutatip Boonsombat; Somsak Ruchirawat; Tanatorn Khotaviv...
• Keywords: Phototoxicity

Abstract Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence absence of UVA irradiation. However, structure–activity relationship on this scaffold remains lacking. Herein, a series psoralen with various C-5 substituents were synthesized evaluated vitro dark light-activated cytotoxicity against three breast cell lines: MDA-MB-231, T47-D, SK-BR-3. The type dramatically impacted activity, 4-bromobenzyl amide derivative ( 3c ) exhibiting highest T47-D (IC 50 = 10.14 µM), comparable to those reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 lapatinib 9.78 µM). On other hand, furanylamide 3g SK-BR-3 cells IC 2.71 µM, which is almost tenfold increase compared parent compound, methoxsalen. Moreover, these showed exceptional selectivity towards HER2+ (SK-BR-3) over HER2− (MDA-MB-231) lines, correlates results from molecular docking study, revealing that formed favorable interactions within active site HER2. Additionally, morphology suggested significant was related induction apoptosis. Most possess acceptable physicochemical properties suitable being further developed as novel agent future.