Figures & data
Figure 1. Structures of some reported isatin-bearing conjugates (I–V), as well as structures for target benzofuran-isatin conjugates (5a–e and 7a–i).
Scheme 1. Synthesis of target conjugates 5a–e; (i) Anhydrous CH3CN/potassium carbonate/reflux 8 h, (ii) Hydrazine hydrate/methanol/reflux 4 h, (iii) Ethanol/drops glacial acetic acid (Cat.)/reflux 3–6 h.
Scheme 2. Synthesis of target benzofurans 7a–i; (i) (R-Br or Ar-Br)/Acetonitrile/KI (Cat.)/potassium carbonate/reflux 3 h, (ii) Ethanol absolute/drops glacial acetic acid (Cat.)/reflux 3–6 h.
Figure 2. Mean % growth inhibition of compounds 5b–d,7a, 7b, 7d and 7g against NCI-55 cancer cell line panel.
Table 1. In vitro Anticancer screening results of compounds 5b–d,7a, 7b, 7d and 7g against fifty-five human tumour cell lines with single dose assay (10−5 M concentration). Data was provided as cell growth inhibition percentage.
Table 2. NCI in vitro screening results (GI50, TGI, and LC50 (μM) of 5d (NSC: D-819833/1) in the five-dose test.
Table 3. Median growth inhibitory concentrationsa (GI50, µM) of in-vitro cancer cell lines subpanel for compound 5d.
Figure 3. Effect of benzofuran–isatin conjugates (5a–e and 7a–i) on the cell viability. (A) SW-620 with hybrids 5a–e and 7a–i, (B) HT-29 with hybrids 5a–e and 7a–i.
Figure 4. IC50 of Compound 5a and 5d. (A) SW-620 with compound 5a, (B) HT-29 with 5a, (C) SW-620 with compound 5d, and (D) HT-29 with 5d.
Figure 5. Impact of 5a and 5d on normal HFF-1 fibroblast cells, upon incubation for 24 h. (A) compound 5a and (B) compound 5d.
Figure 6. (A) AnnexinV/PI apoptosis assay for compound 5a. Tow concentrations (5 and 10 µM) of compound 5a, in addition untreated plate as a control were used to test the apoptotic effect by using Annexin V/PI in SW-620 cell line. Cells were treated with the compound 5a for 24 h. (B) AnnexinV/PI apoptosis assay for compound 5d. Tow concentrations (5 and 10 µM) of compound 5d, in addition untreated plate as a control were used to test the apoptotic effect by using Annexin V/PI in SW-620 cell line. Cells were treated with the compound 5d for 24 h.
Figure 7. (A) Effect of hybrid 5a on anti-apoptotic Bcl2 protein and the level of cleaved PARP. Statistical analysis was performed where the significance of data was assessed at a p values < 0.05. *** p < 0.001; ** p < 0.01 control vs treated. (B) Effect of hybrid 5d on anti-apoptotic Bcl2 protein and the level of cleaved PARP. Statistical analysis was performed where the significance of data was assessed at a p values < 0.05. *** p < 0.001; ** p < 0.01 control vs treated.
