Synthesis of New Chromene Derivatives Targeting Triple-Negative Breast Cancer Cells

Aysha Alneyadi, Zohra Nausheen Nizami, Hanan E. Aburawi, Soleiman Hisaindee, Muhammad Nawaz, Samir Attoub, Gaber Ramadan, Nehla Benhalilou, Mazoun Al Azzani, Yassine Elmahi, Aysha Almeqbali, Khalid Muhammad, Ali H. Eid, Ranjit Vijayan, Rabah Iratni

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Breast cancer continues to be the leading cause of cancer-related deaths among women worldwide. The most aggressive type of breast cancer is triple-negative breast cancer (TNBC). Indeed, not only does TNBC not respond well to several chemotherapeutic agents, but it also frequently develops resistance to various anti-cancer drugs, including taxane mitotic inhibitors. This necessitates the search for newer, more efficacious drugs. In this study, we synthesized two novel chromene derivatives (C1 and C2) and tested their efficacy against a battery of luminal type A and TNBC cell lines. Our results show that C1 and C2 significantly and specifically inhibited TNBC cell viability but had no effect on the luminal A cell type. In addition, these novel compounds induced mitotic arrest, cell multinucleation leading to senescence, and apoptotic cell death through the activation of the extrinsic pathway. We also showed that the underlying mechanisms for these actions of C1 and C2 involved inhibition of microtubule polymerization and disruption of the F-actin cytoskeleton. Furthermore, both compounds significantly attenuated migration of TNBC cells and inhibited angiogenesis in vitro. Finally, we performed an in silico analysis, which revealed that these novel variants bind to the colchicine binding site in β-tubulin. Taken together, our data highlight the potential chemotherapeutic properties of two novel chromene compounds against TNBC.

Original languageEnglish
Article number2682
JournalCancers
Volume15
Issue number10
DOIs
Publication statusPublished - May 2023

Keywords

  • apoptosis
  • chromenes
  • microtubules
  • mitotic slippage
  • multinucleation
  • senescence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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