Two new asymmetrically substituted 1,3,5- triazacyclohexanes: Synthesis, structural characterisation, Hirshfeld surface analysis, DFT calculations, network pharmacology- and molecular docking-based approach to explore the anti-breast-cancer potential

Khawla Belazizia, Ouided Benslama, Rafika Bouchene, Fadila Berrah, Randolf Köhn, Gabriele Kociok-Kohn, Mahmoud Chebbah, Mustapha Bouhenguel, Ahcene Bouchemma

Research output: Contribution to journalArticlepeer-review

Abstract

Two new triazacyclohexanes with two different N-substitutents, 1,3-dicyclopentyl-5-(4-fluorophenyl)-1,3,5-triazinane (I) and 1-cyclopentyl-3,5-bis(4-fluorophenyl)-1,3,5-triazinane (II) have been synthesized through a single condensation reaction followed by separation through selective crystallization. The isolated compounds are stable in the solid state or hydrocarbon solution but slowly convert to differently substituted triazacyclohexanes in more polar chloroform, dichloromethane, or acetonitrile solution. The characterization of these two compounds was carried out using various spectroscopic methods, including FT-IR, UV-Vis, (1H, 13C, 19F, 15N) NMR and single-crystal X-ray diffraction analysis. A theoretical study of the two new compounds in the crystal conformation has been performed with DFT (density functional theory) at B3LYP level using 6-311G + (d, p) basis set. In addition, this study explores the therapeutic potential of (I) and (II) as inhibitors of the HTR2A receptor in breast cancer. Initial target prediction identified 105 potential targets for (I) and 107 for (II), revealing 72 common targets with 67 of these targets associated with breast cancer. Subsequent protein-protein interaction analysis emphasized HTR2A as the central hub gene. Enrichment analysis highlighted key biological processes and pathways related to breast cancer. Molecular docking studies demonstrated favorable interactions between (I), (II) and HTR2A. Drug-likeness and ADMET properties indicate the drug-like potential of both compounds. The results suggest that (I) and (II) are promising candidates for targeting serotonin signaling pathways in breast cancer, potentially enhancing therapeutic strategies.
Original languageEnglish
Article number141662
JournalJournal of Molecular Structure
Early online date5 Feb 2025
DOIs
Publication statusE-pub ahead of print - 5 Feb 2025

Data Availability Statement

CCDC 2391453 and 2391454 contains the supplementary crystallographic data for (I) and (II) , respectively. These data can be obtained free of charge

Funding

The authors would like to thank the Algerian MESRS (Ministère de l'Enseignement Supérieur et de la Recherche Scientifique) for the Financial support.

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