Eco-friendly synthesis, docking study, pharmacokinetics studies, and anti-proliferative evaluation of pyrimidine derivatives as dual Topoisomerase II and HSP90 inhibitors

Tantawy, Eman S.; Shehab, Wesam S.; Abo Elenin, Omnia M.; Assy, Mohamed G.; Elsayed, Doaa A.

doi:10.21608/ejchem.2025.357210.11244

Eco-friendly synthesis, docking study, pharmacokinetics studies, and anti-proliferative evaluation of pyrimidine derivatives as dual Topoisomerase II and HSP90 inhibitors

Articles in Press

Document Type : Original Article

Authors

Department of Chemistry, Faculty of Science, Zagazig University, Zagazig 44519 Egypt.

10.21608/ejchem.2025.357210.11244

Abstract

Manganese oxide nanoparticles (Mn3O₄-NPs) were used as a heterogeneous nano catalyst in this work to create a novel series of pyrimidine derivatives in an ecologically acceptable manner. Simple and easily accessible starting ingredients were used in a one-pot, multicomponent reaction as part of the synthetic approach. Co-precipitation was used to create the Mn3O₄-NPs, and XRD and SEM were used to verify their crystalline structure and nanoscale shape. FT-IR, UV-visible, ¹H NMR, and elemental CHN analysis were among the spectroscopic methods used to establish the structural identity of the synthesized pyrimidine derivatives. The MTT test was used to assess the newly synthesized compounds' anticancer potential in vitro against human cancer cell lines. The compounds' selectivity was also evaluated by measuring their cytotoxicity to normal cells. Several derivatives of the investigated drugs showed low IC₅₀ values and strong antiproliferative action. Molecular docking experiments were conducted against Topoisomerase II and Heat Shock Protein 90 (HSP90), two important cancer-related enzymes, in order to investigate the molecular interactions at the target level. The possible mechanism of anticancer activity was supported by the docking studies, which showed substantial binding affinities and advantageous interactions with important active site residues.

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