2. Academic Validation
  3. Novel psoralen derivatives as anti-breast cancer agents and their light-activated cytotoxicity against HER2 positive breast cancer cells

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

  • Sci Rep. 2022 Aug 5;12(1):13487. doi: 10.1038/s41598-022-17625-x.
Chiphada Aekrungrueangkit 1,  Sirilak Wangngae 2,  Anyanee Kamkaew 2,  Ruchuta Ardkhean 3,  Sanit Thongnest 4 5,  Jutatip Boonsombat 6 7,  Somsak Ruchirawat 4 5 8,  Tanatorn Khotavivattana 9
Affiliations

Affiliations

  • 1 Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 2 School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
  • 3 Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.
  • 4 Chulabhorn Research Institute, Bangkok, 10210, Thailand.
  • 5 Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok, Thailand.
  • 6 Chulabhorn Research Institute, Bangkok, 10210, Thailand. jutatip@cri.or.th.
  • 7 Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok, Thailand. jutatip@cri.or.th.
  • 8 Program in Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.
  • 9 Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand. tanatorn.k@chula.ac.th.
PMID: 35931753 DOI: 10.1038/s41598-022-17625-x
Abstract

Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast Cancer activity both in the presence and the absence of UVA irradiation. However, the structure-activity relationship on this scaffold remains lacking. Herein, a series of psoralen derivatives with various C-5 substituents were synthesized and evaluated for their in vitro dark and light-activated cytotoxicity against three breast Cancer cell lines: MDA-MB-231, T47-D, and SK-BR-3. The type of substituents dramatically impacted the activity, with the 4-bromobenzyl amide derivative (3c) exhibiting the highest dark cytotoxicity against T47-D (IC50 = 10.14 µM), with the activity comparable to those of the reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 µM; lapatinib 9.78 µM). On the other hand, the furanylamide 3g exhibits the highest phototoxicity against SK-BR-3 cells with the IC50 of 2.71 µM, which is almost tenfold increase compared to the parent compound, methoxsalen. Moreover, these derivatives showed exceptional selectivity towards HER2+ (SK-BR-3) over the HER2- (MDA-MB-231) breast Cancer cell lines, which correlates well with the results from the molecular docking study, revealing that 3g formed favorable interactions within the active site of the HER2. Additionally, the cell morphology of SK-BR-3 cells suggested that the significant phototoxicity was related to induction of cell Apoptosis. Most of the synthesized psoralen derivatives possess acceptable physicochemical properties and are suitable for being further developed as a novel anti-breast Cancer agent in the future.

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