Comparative evaluation of new dihydropyrimidine and dihydropyridine derivatives perturbing mitotic spindle formation

摘要

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(1 H )-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.