Synthesis and Evaluation of Novel Carboxamides Capable of Causing Centrosome Declustering and Apoptosis in Breast Cancer Cells
Type
ArticleAuthors
Farrukh, Usama B.Bilal, Aishah
Zahid, Huda

Iqbal, Maheen
Manzoor, Safia
Firdous, Farhat
Furqan, Muhammad
Azeem, Muhammad
Emwas, Abdul-Hamid M.

Alazmi, Meshari

Gao, Xin

Zaib Saleem, Rahman Shah

Faisal, Amir
KAUST Department
Computer, Electrical and Mathematical Sciences and Engineering Division King Abdullah University of Science and Technology Thuwal 23955-6900, Kingdom of Saudi ArabiaStructural 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
Date
2022-04-19Embargo End Date
2023-04-19Permanent link to this record
http://hdl.handle.net/10754/676393
Metadata
Show full item recordAbstract
The 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 deathCitation
Farrukh, 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.202104218Sponsors
Supported by Higher Education Commission, Pakistan (NRPU-5914) and LUMS Faculty Initiative Funds (FIF-222 and FIF-533)Publisher
WileyJournal
ChemistrySelectAdditional Links
https://onlinelibrary.wiley.com/doi/10.1002/slct.202104218ae974a485f413a2113503eed53cd6c53
10.1002/slct.202104218