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.

Autor: Aljuhani A; Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: ateyatallah@hotmail.com., Nafie MS; 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., Albujuq NR; Department of Chemistry, School of Science, The University of Jordan, Amman 11942, Jordan. Electronic address: n.albujuq@ju.edu.jo., Hourani W; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan. Electronic address: Whourani@philadelphia.edu.jo., Albelwi FF; Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: fbalawi@taibahu.edu.sa., Darwish KM; 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., Samir Ayed A; Zoology Department, Faculty of Science, Suez Canal University, Ismailia, P.O. 41522, Egypt. Electronic address: Aya_Abdul-Latif@science.suez.edu.eg., Reda Aouad M; Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: aouadmohamedreda@yahoo.fr., Rezki N; Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia. Electronic address: nadjetrezki@yahoo.fr.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107827. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1016/j.bioorg.2024.107827
Abstrakt: 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, 1 H, 13 C NMR, and elemental analysis). The hybrid click adducts 4b, 4 h, and 6c displayed cytotoxic potency (IC 50 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 (IC 50 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 IC 50 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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