Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study

Figures & data

Figure 1. Reported EGFR inhibitors and antitumour agents, and design of the newly synthesized 2-styrylquinolines.

Scheme 1. Synthesis of the designed 2-styryl-4-quinoline carboxylic acids, and 1,3,4-thiadiazoles 3a,b and 4a,b.

Scheme 2. Synthesis of compounds 5a,b–9a,b.

Figure 2. Relative viability of cells (%) against concentration of the newly synthesized compounds.

Table 1. In vitro antitumour activity of the tested compounds.

Compound no.	In vitro cytotoxicity IC50 (µg/ml)^a
	HepG2	HCT116
3a	9.8 ± 0.20	9.0 ± 0.35
3b	17.2 ± 1.04	14.8 ± 0.89
4a	9.0 ± 0.19	14.2 ± 0.67
4b	7.7 ± 0.15	8.8 ± 0.26
6a	82.9 ± 4.64	96.6 ± 5.40
6b	>100	>100
7a	46.1 ± 2.81	49.7 ± 3.00
7b	72.8 ± 3.82	61.4 ± 3.76
8a	26.2 ± 1.79	16.0 ± 0.88
8b	43.7 ± 2.66	52.6 ± 3.92
9a	65.4 ± 3.18	57.3 ± 3.07
9b	>100	93.1 ± 5.64
5-FU	7.9 ± 0.17	5.3 ± 0.32
Afatinib	5.4 ± 0.25	11.4 ± 1.26

^a IC₅₀, compound concentration required to inhibit tumour cell proliferation by 50%.

IC₅₀, (μg/ml): 1–10 (very strong), 11–25 (strong), 26–50 (moderate), 51–100 (weak), above 100 (non-cytotoxic).

Table 2. IC₅₀ values of the designed compounds toward EGFR kinase and docking interaction energy.

Compound no.	Enzymatic. IC50 (μM)^a	Docking interaction energy (kcal/mol)
3a	2.23	–18.54
3b	8.01	–
4a	8.78	–
4b	1.11	–20.89
8a	16.01	–
Sorafenib	1.14	–
Erlotinib	0.10	–29.01

^a Data represent mean ± SD, n = 3, *p < .05.

Figure 3. Three-dimensional interactions of erlotinib (upper left panel), compounds 4b (lower left panel), and 3a (lower right panel) with the receptor pocket of EGFR kinase. Hydrogen bonds are shown as green line. Upper right panel shows superimposition of compounds 4b (green coloured) and 3a (yellow coloured) on erlotinib (red coloured) inside the pockets of the active site.