Comparative Evaluation of New Dihydropyrimidine and Dihydropyridine Derivatives Perturbing Mitotic Spindle Formation

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2018 Oct 17

PMID 30325216

Citations 2

Authors

Magdalena Peruzynska

Katarzyna Piotrowska

Marta Tkacz

Mateusz Kurzawski

Lukasz Struk

Aleksandra Borzyszkowska

Tomasz J Idzik

Jacek G Sosnicki

Marek Drozdzik

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Co-Administration of Paclitaxel with Novel Pyridine and Benzofuran Derivatives that Inhibit Tubulin Polymerisation: A Promising Anticancer Strategy.

Peruzynska M, Birger R, Klos P, Kwiecien H, Struk L, Sosnicki J Pharmaceutics. 2025; 17(2).

PMID: 40006590 PMC: 11859455. DOI: 10.3390/pharmaceutics17020223.

Antiproliferative Activity of Some Newly Synthesized Substituted Nicotinamides Candidates Using Pyridine-2(1) thione Derivatives as Synthon.

Elnaggar D, Mohamed A, Abdel Hafez N, Azab M, Elasasy M, Awad H ACS Omega. 2022; 7(12):10304-10316.

PMID: 35382307 PMC: 8973085. DOI: 10.1021/acsomega.1c06951.

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1)-thiones.

Peruzynska M, Borzyszkowska-Ledwig A, Sosnicki J, Struk L, Idzik T, Maciejewska G Int J Mol Sci. 2021; 22(5).

PMID: 33671106 PMC: 7957618. DOI: 10.3390/ijms22052462.