Synthesis, DFT calculations, and anti-proliferative evaluation of pyrimidine and selenadiazolopyrimidine derivatives as dual Topoisomerase II and HSP90 inhibitors.

ABSTRACT: Novel series of aminopyrimidines bearing a biologically active cyclohexenone 3a-f and oxo-selaneylidene moiety 4, besides selenadiazolopyrimidines (5a-e and 7), were synthesised using 5,6-diaminouracils as starting materials. Compound 3a exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC₅₀ 14.31 ± 0.83 µM), A-549 (IC₅₀ 30.74 ± 0.76 µM), and MCF-7 (IC₅₀ 27.14 ± 1.91 µM). Also, it was four times more selectively cytotoxic against WI-38 cell lines than doxorubicin. Furthermore, Topoisomerase II (IC₅₀ 4.48 ± 0.65 µM) and HSP90 (IC₅₀ 1.78 ± 0.11 µM) were both strongly inhibited in vitro by 3a. The cell cycle was halted at the G1-S phase, and total apoptotic cell

SUBMITTER: El-Kalyoubi S 

PROVIDER: S-EPMC10088926 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature