Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent

Sana Iqbal, Farhat Firdous, Muhammad Furqan, Aishah Bilal, Salman Fozail, Sebastian Öther Gee Pohl, Nora Julia Doleschall, Kevin B. Myant, Upendra Singh, Abdul Hamid Emwas, Mariusz Jaremko, Amir Faisal*, Rahman Shah Zaib Saleem

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.

Original languageEnglish (US)
Article number107094
JournalBioorganic Chemistry
Volume143
DOIs
StatePublished - Feb 2024

Keywords

  • Anticancer
  • Bis-amide
  • Microtubule stabilizing agents
  • Mouse organoid and human organoid models
  • Tubulin polymerization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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