Fig 1.
Examples of Pgp inhibitors.
Fig 2.
Design of Pgp inhibitors by re-scaffolding of the linker region of curcumin and verapamil.
Fig 3.
Reagents and Conditions: (a) Acetic anhydride, sodium acetate, heat. (b) Aniline, acetic acid, sodium acetate, 110°C, 24 hr. (c) Ammonium acetate, pyridine, 110°C, 18 hr. (d) n-PrNH2, EtOH, r.t., 2h.
Table 1.
Structure and codes of the synthesized oxazolones and imidazolones.
Fig 4.
(A) The effect of test compounds on the activity of P-glycoprotein efflux pump cell free isolated recombinant P-gp protein and (B) within LS-174T cells.
The influence of test compounds on the cellular pharmacokinetics via inhibiting the activity of Pgp pump. Verapamil (VRP) is a standard direct Pgp blocker. Sod Vanadate is a standard ATPase inhibitor. Curcumin is the prototype compound in the design. The asterisk (*) denotes significant difference from control.
Table 2.
Cytotoxic Activity of synthesized compounds against LS174T CRC cell lines.
Fig 5.
The effect of serial equitoxic concentrations (ratio 1:100) of Cur3 (A), and 10 μM (B), and serial concentration of Cur1-12V (ratio 1:100) (C) on the cytotoxicity of PTX in LS-174T cells.
Cells were exposed to serial dilution of PTX (●), Chemosensetizer (▼) or their combination (○) for 72 h. Cell viability was determined using SRB assay.
Table 3.
Chemomedulatory effects of test compounds on the cytotoxicity parameters of PTX against LS-174T cell line.
Fig 6.
The effect of serial equitoxic concentrations (ratio 1:100) of Cur3 (A), and 10 μM (B), and serial concentration of Cur1-12V (ratio 1:100) (C) on the cytotoxicity of PTX in HCT-116 cells.
Cells were exposed to serial dilution of PTX (●), Chemosensetizer (▼) or their combination (○) for 72 h. Cell viability was determined using SRB assay.