Synthesis, antitumor activity evaluation of some new N-aroyl-α,β-unsaturated piperidones with fluorescence

Figures & data

Figure 1. The structures of 3,5-bis(benzylidene)-4-piperidones synthesized are shown.

Figure 2. Binding sites A and B and designation of the torsion angles θ₁ and θ₂ of the compounds synthesized.

Scheme 1 Synthetic chemical pathway of compounds in series 1–3. The reagents used in the syntheses were as follows: (I) 2-bromo-4,5-dimethoxy-benzaldehyde/CH₃COOH/dry HCl; (II) 4-dimethylamino-benzaldehyde/CH₃COOH/dry HCl; (III) 4-trifluoromethyl-benzaldehyde/CH₃COOH/dry HCl; (IV) 4-nitrobenzoyl chloride/NaOH/ClCH₂CH₂Cl/K₂CO₃/tetrabutylammonium bromide or 4-methylbenzene sulfonyl chloride/4-acetamidobenzenesulfonyl chloride/4-nitrobenzenesulfonyl/NaOH/ClCH₂CH₂Cl/tetrabutylammonium bromide/CH₃COOH.

Table 1. Cytotoxicity of 1a–1e, 2a–2e and 3a–3e against human SK-BR-3, PG-BE1, NCI-H460, MIA PaCa-2 and SW1990 cell lines.

	IC50 (µM)
Compound	SK-BR-3	PG-BE1	NCI-H460	MIA PaCa-2	SW1990
1a	4.38 ± 0.48	1.31 ± 0.04	0.960 ± 0.108	0.377 ± 0.027	1.91 ± 0.37
1b	3.19 ± 0.53	0.382 ± 0.098	0.402 ± 0.056	0.167 ± 0.017	0.978 ± 0.496
1c	10.8 ± 1.9	3.16 ± 0.73	3.44 ± 0.67	1.24 ± 0.35	3.66 ± 0.28
1d	2.86 ± 0.35	1.77 ± 0.28	1.39 ± 0.51	0.29 ± 0.06	1.72 ± 0.37
1e	23.1 ± 1.1	2.27 ± 0.54	1.41 ± 0.30	1.33 ± 0.07	4.74 ± 0.76
2a	64.0 ± 10.5	11.3 ± 2.77	11.8 ± 3.6	8.23 ± 0.33	36.7 ± 5.0
2b	>100	>100	>100	>100	>100
2c	13.6 ± 1.5	23.4 ± 2.4	9.66 ± 3.79	8.82 ± 1.48	12.6 ± 3.4
2d	>100	>100	>100	>100	>100
2e	>100	>100	>100	>100	>100
3a	0.843 ± 0.092	0.661 ± 0.046	1.04 ± 0.21	0.417 ± 0.094	1.94 ± 0.24
3b	3.70 ± 0.14	4.08 ± 0.32	3.38 ± 0.11	0.230 ± 0.016	1.51 ± 0.48
3c	4.40 ± 0.15	1.75 ± 0.44	0.544 ± 0.243	0.593 ± 0.132	3.69 ± 0.21
3d	1.12 ± 0.24	0.820 ± 0.085	0.321 ± 0.081	0.353 ± 0.016	0.755 ± 0.553
3e	0.417 ± 0.080	0.565 ± 0.042	0.126 ± 0.031	0.107 ± 0.006	0.365 ± 0.109
5-FU	1297 ± 330	94.3 ± 23.9	35.8 ± 11.6	102 ± 9	474 ± 96

Figure 3. The inhibitory effect of compounds 1a–1e and 3a–3e against five human carcinoma cell lines.

Figure 4. The ORTEP figure of 1e (displacement ellipsoids with 30% probability, omitting two molecules of CHCl₃).

Figure 5. (A) The tumor growth inhibition of compound 1b against nude mice with PG-BE1 xenograft (in the light of tumor volume). (B) The effect of compound 1b on the body weight of nude mice with PG-BE1 xenograft.

Figure 6. (A) The fluorescence spectra of 1a–1e at room temperature. (B) The fluorescence spectra of 2a–2e at room temperature. (C) The fluorescence spectra of 3a–3e at room temperature.