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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

Anti-cancer Activity of New Phosphoramide-functionalized Graphene Oxides: An Experimental and Theoretical Evaluation

Author(s): Khodayar Gholivand*, Mohammad Faraghi, Mahsa Pooyan, Leila Sarmadi Babaee, Rahime Eshaghi Malekshah, Foroogh Pirastehfar and Mohammad Vahabirad

Volume 30, Issue 30, 2023

Published on: 25 November, 2022

Page: [3486 - 3503] Pages: 18

DOI: 10.2174/0929867330666221027152716

Price: $65

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Abstract

Background: Graphene oxide (GO)-based systems are among the drug delivery systems and have drawn a lot of interest in the field of medicine.

Methods: In this work, two novel phosphoramides with the formulas of (NHCHCH2C(CH3)2NHC(CH3)2CH2P(S)(OEt)2 (L1) and (NHCHCH2C(CH3)2 NHC (CH3)2CH2P (O) (NHC6H5) (OC5H6) (L2) were synthesized and characterized by spectroscopic methods. Then, graphene oxide (GO) was functionalized by L1 and L2. FT-IR, XRD, FE- SEM/ MAP, and Zeta potential analyses were applied to confirm the synthesis of phosphoramide-functionalized graphene oxides (GO-L1 and GO-L2). Cytotoxicity of synthesized compounds was evaluated against breast cancer cell line (SK-BR-3) using MTT assay. Moreover, the flow cytometry assay was performed to evaluate the cell death mechanisms.

Results: The results showed that GO-L1 and GO-L2 had a more inhibitory effect against cancer cells than that of L1 and L2, and GO-L2 showed the highest cytotoxicity with an IC50 value of 38.13 μg/ml. Quantum calculations were employed to optimize structures. HOMO and LUMO energy values and physical adsorption of synthesized compounds were obtained by the DMol3 module in the Material Studio 2017. The docking studies were used to investigate the binding of L1, L2, GO-L1, and GO-L2 to DNA polymerase IIα.

Conclusion: Anticancer activity of phosphoramide compounds was increased after attachment on the GO surface, and the docking studies' results were in good accordance with the experimental cytotoxicity results.

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