Synthesis, anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies

Figures & data

Figure 1. Reported and proposed quinazoline–isatin conjugates with antitumor and tyrosine kinase inhibitory activity.

Scheme 1. Synthesis of 2-[(3-substituted-4(3H)-quinazolinon-2-yl)thio]acetohydrazides 11–15.

Scheme 2. Synthesis of quinazoline-isatin conjugates 16–34.

Table 1. In vitro antitumor activity of the newly synthesized compounds 16–34.

Compounds	MDA-MB-231^a IC50 (μM)^c	LOVO^b IC50 (μM)^c
16	16.23 ± 0.32	33.97 ± 0.26
17	14.97 ± 0.37	23.98 ± 0.06
18	12.38 ± 0.3	21.46 ± 0.13
19	12.31 ± 0.11	17.53 ± 0.04
20	16.82 ± 0.13	14.80 ± 0.1
21	14.48 ± 0.03	14.21 ± 0.06
22	18.33 ± 0.01	14.14 ± 0.06
23	17.14 ± 0.01	13.39 ± 0.23
24	11.50 ± 0.36	20.39 ± 0.02
25	11.41 ± 0.07	12.00 ± 0.05
26	11.80 ± 0.02	23.62 ± 0.01
27	18.05 ± 0.04	12.80 ± 0.03
28	37.41 ± 0.06	14.20 ± 0.09
29	38.67 ± 0.04	14.00 ± 1.02
30	13.77 ± 0.4	14.12 ± 0.06
31	10.38 ± 0.22	9.91 ± 0.12
32	18.35 ± 0.14	16.51 ± 0.15
33	20.21 ± 0.05	14.37 ± 0.46
34	20.06 ± 0.11	15.77 ± 0.16
5-FU	70.28 ± 0.2	15.23 ± 0.09
Erlotinib	22.24 ± 0.22	25.31 ± 0.12

^a Aggressive human MDA-MB-231 (representative triple negative breast cancer cells with high metastasis potential).

^b Aggressive human LOVO colon cell line (type IV metastasized colon cancer).

^c IC₅₀: concentration of the compound (μM) that produced 50% inhibition of cell growth inhibition after 48 h of treatment.

Figure 2. EGFR (left panel; green color) of MDA-MB-231 breast cell line and (right panel) MDA-MB-231 breast cell line after treatment with compound 31.

Figure 3. MDA-MB-231 breast cancer cell line was treated with compound 31 (right panel), which displayed an increased percentage of fluorescein isothiocyanate annexin V (Annexin V–FITC), and untreated control cells (left panel).

Figure 4. Docking of compound 31 (left panel) and superposition with erlotinib (right panel) in the receptor pocket of EGFR kinase. Compound 31 and erlotinib are shown in green and cyan, respectively.

Figure 5. Docking of compound 28 (left panel) and superposition with erlotinib (right panel) in the receptor pocket of EGFR kinase. Compound 28 and erlotinib are shown in yellow and cyan, respectively.