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Drug Design, Development and Therapy Volume 13, 2019 - Issue
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Original Research

Dexibuprofen amide derivatives as potential anticancer agents: synthesis, in silico docking, bioevaluation, and molecular dynamic simulation

Zaman Ashraf1 Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan
,
Tariq Mahmood1 Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan
,
Mubashir Hassan2 Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea
,
Samina Afzal3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakria University, Multan, Pakistan
,
Hummera Rafique4 Department of Chemistry, University of Gujrat, Gujrat, Pakistan
,
Khurram Afzal3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakria University, Multan, Pakistan
&
Jalifah Latip5 Department of Pharmaceutical Chemistry, School of Chemical Sciences & Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia, [email protected]Correspondence[email protected]
 show all
Pages 1643-1657 | Published online: 14 May 2019

Figures & data

Table 1 Brine shrimp lethality assay and antitumor activity of synthesized dexibuprofen amides (4a–j)

Table 2 Anticancer activity of synthesized dexibuprofen amides (4a–j) against breast carcinoma cell line (MCF-7) and human normal epithelial breast cell line (MCF-12A)

Table 3 Ulcerogenic activity of most potent amides 4e and 4g

Figure 1 Overview of crystal structure of BRCA1.

Notes: Red color shows domain 1 with residual length while blue color shows domain 2 with residual length. Two circular depictions in green and grey colors represent the chlorine and nickel metals, respectively.
Figure 1 Overview of crystal structure of BRCA1.

Figure 2 The hierarchical patterns of domains 1 and 2 of target protein BRCA1.

Notes: Red color shows domain 1 while blue color shows domain 2. You can add A with red color and B with blue color.
Figure 2 The hierarchical patterns of domains 1 and 2 of target protein BRCA1.

Table 4 Biological properties of synthesized dexibuprofen amides (4a–j)

Table 5 Toxicity risk assessment evaluations of dexibuprofen amides (4a–j)

Table 6 Docking energy evaluation of synthesized amides (4a–j) against BRCA1

Figure 3 Docking complex of 4e against BRCA1.

Notes: The ligand structure is shown in Berghaus blue while the functional groups such as oxygen, nitrogen and chlorine are displayed in red, blue and yellow colors, respectively. The active site residues are depicted in dark red and labeled with black. The amino acid which participates in hydrogen bonding is highlighted in green along with bonding distance in angstrom (Å). The receptor protein is displayed in line format in light grey.
Figure 3 Docking complex of 4e against BRCA1.

Figure 4 Docking complex of 4g against BRCA1.

Notes: The ligand structure is displayed in Berghaus blue while the functional groups such as oxygen, nitrogen and chlorine are displayed in red, blue and yellow colors, respectively. The active site residues are depicted in dark red and labeled with black. The amino acid which participates in hydrogen bonding is highlighted in green along with bonding distance in angstrom (Å). The receptor protein is displayed in line format in light grey.
Figure 4 Docking complex of 4g against BRCA1.

Figure 5 Docking complexes of standard drugs (erlotinib and doxorubicin) against BRAC1.

Figure 5 Docking complexes of standard drugs (erlotinib and doxorubicin) against BRAC1.

Figure 6 Docking complexes of the synthesized dexibuprofen derivatives 4a–j.

Figure 6 Docking complexes of the synthesized dexibuprofen derivatives 4a–j.

Figure 7 RMSD graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Abbreviation: RMSD, root mean square deviation.
Figure 7 RMSD graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Figure 8 RMSF graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Abbreviation: RMSF, root mean square fluctuation.
Figure 8 RMSF graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Figure 9 Rg graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Abbreviation: Rg, radius of gyration.
Figure 9 Rg graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Figure 10 SASA graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

Abbreviation: SASA, solvent-accessible surface area.
Figure 10 SASA graphs of 4e and 4g docked complexes are shown in purple and blue respectively from 0–10,000 ps time scale.

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