Synthesis and Evaluation of Novel Carboxamides Capable of Causing Centrosome Declustering and Apoptosis in Breast Cancer Cells
AuthorsFarrukh, Usama B.
Emwas, Abdul-Hamid M.
Zaib Saleem, Rahman Shah
KAUST DepartmentComputer, Electrical and Mathematical Sciences and Engineering Division King Abdullah University of Science and Technology Thuwal 23955-6900, Kingdom of Saudi Arabia
Structural and Functional Bioinformatics Group
Computer Science Program
Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Computational Bioscience Research Center (CBRC)
Imaging and Characterization Core Lab
Embargo End Date2023-04-19
Permanent link to this recordhttp://hdl.handle.net/10754/676393
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AbstractThe fragility of cancer cells at the time of mitosis has served as an important target for the development of many successful chemotherapeutic agents. Many cancers cells have supernumerary centrosomes that they cluster during mitosis to form bipolar spindles. Inhibition of centrosome clustering in these cells results in multipolar spindle formation and apoptotic cell death, providing an opportunity to selectively target a subset of cancers with centrosome amplification. In the current work, we report synthesis of 29 novel tethered biaryls and biological evaluation of their ability to inhibit centrosome clustering in breast cancer cells (BT-549). We have identified N-benzhydryl-5-nitrofuran-2-carboxamide (5 h) as a centrosome declustering compound. 5 h has potent antiproliferative activity in centrosome amplified BT-549 cells with GI50 value of 1.81±0.19 μM (n=2). Treatment of BT-549 cells with 5 h causes centrosome declustering resulting in mitotic arrest due to multipolar spindle formation and misaligned chromosomes which ultimately leads to apoptotic cell death
CitationFarrukh, U. B., Bilal, A., Zahid, H., Iqbal, M., Manzoor, S., Firdous, F., Furqan, M., Azeem, M., Emwas, A., Alazmi, M., Gao, X., Saleem, R. S. Z., & Faisal, A. (2022). Synthesis and Evaluation of Novel Carboxamides Capable of Causing Centrosome Declustering and Apoptosis in Breast Cancer Cells. ChemistrySelect, 7(15). Portico. https://doi.org/10.1002/slct.202104218
SponsorsSupported by Higher Education Commission, Pakistan (NRPU-5914) and LUMS Faculty Initiative Funds (FIF-222 and FIF-533)