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. 2025 May 16;19(1):131.
doi: 10.1186/s13065-025-01489-z.

Fe3O4@SiO2-SnCl4-promoted synthesis, cytotoxic evaluation, molecular docking, and MD simulation of some indenopyrido[2,3-d]pyrimidine derivatives

Leila Emami  1 , Ladan Baziyar  2 , Al-Anood Mohammad Al-Dies  3 , Sara Sadeghian  2 , Bi Bi Fatemeh Mirjalili  4 , Zeinab Faghih  1 , Sajad Khorasani  1 , Leila Zamani  1 , Soghra Khabnadideh  5   6
Affiliations

Fe3O4@SiO2-SnCl4-promoted synthesis, cytotoxic evaluation, molecular docking, and MD simulation of some indenopyrido[2,3-d]pyrimidine derivatives

Leila Emami et al. BMC Chem. .

Abstract

In this study, an efficient and environmentally friendly method for the one-pot synthesis of indenopyrido[2,3-d]pyrimidine derivatives was developed using Fe3O4@SiO2-SnCl4 nanoparticles as a catalyst. Indenopyrido[2,3-d]pyrimidines (4a-4j) were synthesized via three-component couplings of 6-amino-2-(methylthio)pyrimidin-4(3H)-one, 1,3-indanedione, and aldehydes in water as the solvent. In this reaction, Fe3O4@SiO2-SnCl4 demonstrated a highly catalytic nature, an easy handling procedure, short reaction times, recyclability exploitation, and excellent yields. The cytotoxic activities of the synthesized indenopyrido[2,3-d] pyrimidines analogues were evaluated against three cancer cell lines; MCF-7 (breast carcinoma), A549 (lung non-small cell carcinoma), and SKOV3 (ovarian carcinoma) using MTT assay. Additionally, molecular docking studies and molecular dynamics (MD) simulation of the investigated compounds was performed to verify their binding modes toward EGFR kinase receptor as the possible targets. This analysis aimed to predict the antitumor mechanisms of the synthesized compounds. The binding free energy values of the compounds showed a satisfactory correlation with their cytotoxic activities.

Keywords: Cytotoxic activity; Indenopyrido[2,3-d]pyrimidine; MD Simulation; Molecular docking.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Indeno [1, 2-d] pyrimidine and pyrido[2,3-d]pyrimidines derivatives with anticancer activity
Fig. 2
Fig. 2
Synthesis of indenopyrido[2,3-d]pyrimidines (4a–4j)
Fig. 3
Fig. 3
Proposed mechanism for the synthesis of indenopyrido[2,3-d]pyrimidines in the presence of Fe3O4@SiO2-SnCl4
Fig. 4
Fig. 4
The main interaction of Erlotinib (yellow) and 4f (pink) in the active site of EGFR (PDB ID: 1M17)
Fig. 5
Fig. 5
The structure of 4i surrounded by the key residue in the active site of EGFR
Fig. 6
Fig. 6
The interaction and binding mode of 4f and 4i in the active site of estrogen receptor alpha (ERα) (PDB ID: 3ERT)
Fig. 7
Fig. 7
RMSD of the total system during simulation time
Fig. 8
Fig. 8
RMSF analysis of the protein backbone atoms of the 1M17 in complexes with 4f and 4c ligands
Fig. 9
Fig. 9
Radius of gyration during the simulation process
Fig. 10
Fig. 10
Number of hydrogen bonds between ligands and protein through simulation time
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