AIM: The mitotic spindle plays a key role in cell division which makes it an important target in cancer therapy. In the present study the antiproliferative activity of 4-benzyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione (1) and its pyridine bioisoster (2) were evaluated and compared with monastrol (MON), the first known cell-permeable small molecule which disrupts bipolar spindle formation by inhibiting Eg5-kinesin activity. RESULTS: Our data revealed that compound 2 showed higher antiproliferative activity than MON against MCF7 and A375 cell lines and comparable reversible cell cycle inhibition in G2/M phase. However, compound 2 produced distinct phenotype from monoastral spindles, and did not affect Eg5 ATPase activity. CONCLUSION: The activity of compound 2 may suggest its new promising anticancer mechanism (different than MON), targeting other component required for spindle bipolarity.
AIM: The mitotic spindle plays a key role in cell division which makes it an important target in cancer therapy. In the present study the antiproliferative activity of 4-benzyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione (1) and its pyridine bioisoster (2) were evaluated and compared with monastrol (MON), the first known cell-permeable small molecule which disrupts bipolar spindle formation by inhibiting Eg5-kinesin activity. RESULTS: Our data revealed that compound 2 showed higher antiproliferative activity than MON against MCF7 and A375 cell lines and comparable reversible cell cycle inhibition in G2/M phase. However, compound 2 produced distinct phenotype from monoastral spindles, and did not affect Eg5 ATPase activity. CONCLUSION: The activity of compound 2 may suggest its new promising anticancer mechanism (different than MON), targeting other component required for spindle bipolarity.
Entities:
Keywords:
antiproliferative activity; dihydropyridine; dihydropyrimidine; drug design; mitotic spindle inhibitors
Authors: Magdalena Perużyńska; Aleksandra Borzyszkowska-Ledwig; Jacek G Sośnicki; Łukasz Struk; Tomasz J Idzik; Gabriela Maciejewska; Łukasz Skalski; Katarzyna Piotrowska; Paweł Łukasik; Marek Droździk; Mateusz Kurzawski Journal: Int J Mol Sci Date: 2021-02-28 Impact factor: 5.923
Authors: Dina H Elnaggar; Ashraf M Mohamed; Naglaa A Abdel Hafez; Mohamed E Azab; Manar E A Elasasy; Hanem M Awad; Thoraya A Farghaly; Abd El-Galil E Amr Journal: ACS Omega Date: 2022-03-16