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  3. Unveiling the anti-cancer potentiality of phthalimide-based Analogues targeting tubulin polymerization in MCF-7 cancerous Cells: Rational design, chemical Synthesis, and Biological-coupled Computational investigation

Unveiling the anti-cancer potentiality of phthalimide-based Analogues targeting tubulin polymerization in MCF-7 cancerous Cells: Rational design, chemical Synthesis, and Biological-coupled Computational investigation

  • Bioorg Chem. 2024 Dec:153:107827. doi: 10.1016/j.bioorg.2024.107827.
Ateyatallah Aljuhani 1,  Mohamed S Nafie 2,  Nader R Albujuq 3,  Wafa Hourani 4,  Fawzia F Albelwi 5,  Khaled M Darwish 6,  Aya Samir Ayed 7,  Mohamed Reda Aouad 8,  Nadjet Rezki 9
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: ateyatallah@hotmail.com.
  • 2 Department of Chemistry, College of Sciences, University of Sharjah, Sharjah P.O. 27272, United Arab Emirates (UAE); Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, P.O. 41522, Egypt. Electronic address: mohamed.elsayed@sharjah.ac.ae.
  • 3 Department of Chemistry, School of Science, The University of Jordan, Amman 11942, Jordan. Electronic address: n.albujuq@ju.edu.jo.
  • 4 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan. Electronic address: Whourani@philadelphia.edu.jo.
  • 5 Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: fbalawi@taibahu.edu.sa.
  • 6 Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University, New Galala 43713, Egypt. Electronic address: Khaled_darwish@pharm.suez.edu.eg.
  • 7 Zoology Department, Faculty of Science, Suez Canal University, Ismailia, P.O. 41522, Egypt. Electronic address: Aya_Abdul-Latif@science.suez.edu.eg.
  • 8 Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: aouadmohamedreda@yahoo.fr.
  • 9 Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: nadjetrezki@yahoo.fr.
PMID: 39321715 DOI: 10.1016/j.bioorg.2024.107827
Abstract

The present study deals with an anti-cancer investigation of an array of phthalimide-1,2,3-triazole molecular conjugates with various sulfonamide fragments against human breast MCF-7 and prostate PC3 Cancer cell lines. The targeted 1,2,3-triazole derivatives 4a-l and 6a-c were synthesized from focused phthalimide-based alkyne precursors using a facile click synthesis approach and were thoroughly characterized using several spectroscopic techniques (IR, 1H, 13C NMR, and elemental analysis). The hybrid click adducts 4b, 4 h, and 6c displayed cytotoxic potency (IC50 values of 1.49, 1.07, and 0.56 μM, respectively) against MCF-7 cells. On the contrary, none of the synthesized compounds showed apparent cytotoxic efficacy for PC3 cells (IC50 ranging from 9.87- >100 μM). As a part of the mechanism analysis, compound 6c demonstrated a potent inhibitory effect (78.3 % inhibition) of tubulin polymerization in vitro with an IC50 value of 6.53 µM. In addition, biological assays showed that compound 6c could prompt apoptotic cell death and induce G2/M cell cycle arrest in MCF-7 cells. Accordingly, compound 6c can be further developed as an anti-breast Cancer agent through apoptosis-induction.

Keywords

1,2,3-Triazoles; Apoptosis activity; Phthalimides; Sulfonamides; Tubulin inhibitor.

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