New phosphoramides containing 2-amino-1,4-naphthaquinone moiety as anticancer and antibacterial agents: Experimental and theoretical evaluations

In this study, two novel phosphoramides containing 2-Amino-1,4-naphthaquinone, O,O-diethyl (2-naphthaleneyl-1,4-dione)phosphoramidothioate (NPT) and N,N & PRIME;- bis(2-naphthaleneyl-1,4-dione) phenylphosphonic diamide (NPA) as cytotoxic agents, were synthesized and characterized by using spectroscopic methods. The anticancer activities of the synthesized compounds were investigated against the human breast cancer cell line SK-BR-3 and normal cells PC12 using MTT assay. The resulting data showed that NPA with an IC50 value of 6.384 & mu;g/ml had a better inhibitory effect against cancer cells than NPT (IC50 = 10.08 & mu;g/ml). According to the annexin V-FITC/PI results, after treating cancer cells with synthesized compounds for 24 h, the overall population of apoptotic cells increased from 14.96% in the control group to 97.45%, 75.58% in NPA and NPT-treated cells, respectively. Given these results, NPA and NPT have considerable toxicity and apoptosis-inducing ability against SK-BR-3. The cytotoxicity results were supported by a molecular docking study to compute the interactions between synthesized compounds and transcription factor DNA (PDB ID: 1bg1). In order to know the structure-activity relationship (SAR) of synthesized compounds, the values of the quantum-mechanical descriptors were investigated computationally by the DFT method, and the obtained results were then compared with Cyclophosphamide (CY) as a standard anticancer drug. These results were in good accordance with those of in vitro investigation and molecular docking study. Antibacterial study of phosphoramides against Gramnegative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) was carried out MIC, MBC and DDA methods. Additionally, the molecular docking study was performed for the interaction between E. coli betalactamase (PDB: 4HBT) and S. aureus beta-lactamase (PDB: 1MWU) with target compounds, the obtained results showed that these compounds are appropriate ligands for antibacterial activity against Staphylococcus aureus and Escherichia coli bacteria.

Automated summary

Two novel phosphoramides containing 2-Amino-1,4-naphthaquinone, O,O-diethyl (2-naphthaleneyl-1,4-dione)phosphoramidothioate (NPT) and N,N & PRIME;- bis(2-naphthaleneyl-1,4-dione) phenylphosphonic diamide (NPA) were synthesized and characterized. The synthesized compounds exhibited anticancer activities against SK-BR-3 breast cancer cells with NPA showing better inhibitory effect compared to NPT. Additionally, the compounds showed antibacterial activity against Staphylococcus aureus and Escherichia coli.