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An Experimental and Theoretical Approach of a Novel Phosphoramide Containing Naphthoquinone With Potential Cytotoxic and Apoptosis-Inducing Ability Publisher



Gholivand K1 ; Faraghi M1 ; Vahabirad M2 ; Malekshah RE3 ; Narimani S4 ; Roohzadeh R1 ; Fallah N5 ; Jannesar S6 ; Yousefian M7
Authors
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Authors Affiliations
  1. 1. Department of Chemistry, Faculty of Science, Tarbiat Modares University, Tehran, Iran
  2. 2. Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  3. 3. Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Department of chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
  6. 6. Dental Implant Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: Journal of Molecular Structure Published:2025


Abstract

In an attempt to synthesize a new potent cytotoxic and apoptosis-inducing agent against SK-BR-3 breast cancer cells, a new phosphoramide containing naphthoquinone (Diphenyl (1,4-dioxo-1,4-dihydronaphthalen-2-yl)phosphoramidate; A) was synthesized and characterized using some experimental techniques such as IR, 1H NMR, 13C NMR, 31P NMR, and Mass spectroscopies. The obtained data were compared with theoretical FT-IR, 1H NMR, 13C NMR and 31P NMR calculated with density functional theory (DFT), which confirmed that there is a good correlation between them. The cytotoxic activity of A against cancer cell line (SK-BR-3) and normal cell line (MCF10A) were evaluated through an MTT assay. The results showed a dose- and time-dependent anti-cancer activity with IC50 values of 10.3 µM (24 h) and 8.1 µM (48 h). According to the flow cytometry results, A showed great apoptosis-inducing ability at different concentrations (5 µM) (41.88%), 20 µM (72.6%), and 30 µM (79.1%). Moreover, the cells inhibited through the late apoptosis pathway increased as a function of the concentration of A. In order to know the structure-activity relationship (SAR) of the synthesized compound and cyclophosphamide (Cpm), the values of HOMO and LUMO energies, hardness, softness, and electrophilicity index were investigated computationally by DFT-D correction in Material Studio 2017. Additionally, molecular docking simulation was used to compute the interactions between (A or Cpm) and transcription factor STAT3B/DNA complex (PDB ID: 1bg1), indicating A has a considerable anti-cancer potential with docking energy of -101.964 kcal.mol-1 compared with -64.281 kcal.mol-1 for Cpm. © 2024
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