Synthesis and anti-cancer activity evaluation of new aurone derivatives

Figures & data

Figure 1. The chemical structures of (a) chalcone, (b) flavone, (c) aurone, (d) sulfuretin.

Table 1. Some characteristics of the compounds (C1–C10).

C.	Chemical name	R	–OH	M.P. (°C)
C1	2-(3-Hydroxybenzylidene)benzofuran-3-one	H	3	195–19651
C2	2-(4-Hydroxybenzylidene)benzofuran-3-one	H	4	261–26251
C3	5-Methyl-2-(3-hydroxybenzylidene)benzofuran-3-one	5-CH3	3	221–222
C4	5-Methyl-2-(4-hydroxybenzylidene)benzofuran-3-one	5-CH3	4	263–26452
C5	6-Methyl-2-(3-hydroxybenzylidene)benzofuran-3-one	6-CH3	3	195–197
C6	6-Methyl-2-(4-hydroxybenzylidene)benzofuran-3-one	6-CH3	4	250–252
C7	6-Methoxy-2-(3-hydroxybenzylidene)benzofuran-3-one	6-OCH3	3	220–22253
C8	6-Methoxy-2-(4-hydroxybenzylidene)benzofuran-3-one	6-OCH3	4	219–22053
C9	5-Chloro-2-(3-hydroxybenzylidene)benzofuran-3-one	5-Cl	3	199–201
C10	5-Chloro-2-(4-hydroxybenzylidene)benzofuran-3-one	5-Cl	4	270–272

Table 2. Some characteristics of the compounds (D1-D38)..

Compound	-R	^−R′	Position	M.P. (°C)	M.F.
D1	-H	‐H	3	150–151	C23H16O4
D2	-H	‐CH3	3	162–162	C24H18O4
D3	‐H	‐OCH3	3	135–136	C24H18O5
D4	-H	‐Cl	3	134–135	C23H15ClO4
D5	-H	‐NO2	3	195–197	C23H15NO6
D6	-H	‐H	4	150–152	C23H16O4
D7	-H	‐CH3	4	186–188	C24H18O4
D8	-H	‐OCH3	4	180–181	C24H18O5
D9	-H	‐Cl	4	176–177	C23H15ClO4
D10	-H	‐NO2	4	220–221	C23H15NO6
D11	5-CH3	‐H	3	149–150	C24H18O4
D12	5-CH3	‐OCH3	3	173–174	C25H20O5
D13	5-CH3	‐Cl	3	159–161	C25H17ClO4
D14	5-CH3	‐H	4	203–204	C24H18O4
D15	5-CH3	‐OCH3	4	220–221	C25H20O5
D16	5-CH3	‐Cl	4	226–227	C25H17ClO4
D17	6-CH3	‐H	3	139–140	C24H18O4
D18	6-CH3	‐OCH3	3	130–132	C25H20O5
D19	6-CH3	‐Cl	3	179–181	C25H17ClO4
D20	6-CH3	‐H	4	175–176	C24H18O4
D21	6-CH3	‐OCH3	4	204–205	C25H20O5
D22	6-CH3	‐Cl	4	209–210	C25H17ClO4
D23	6-OCH3	‐H	3	136–137	C24H18O5
D24	6-OCH3	‐CH3	3	172–173	C25H20O5
D25	6-OCH3	‐OCH3	3	192–193	C25H20O6
D26	6-OCH3	‐Cl	3	190–192	C24H17ClO5
D27	6-OCH3	‐NO2	3	212–214	C24H17NO7
D28	6-OCH3	‐H	4	197–199	C24H18O5
D29	6-OCH3	‐CH3	4	185–187	C25H20O5
D30	6-OCH3	‐OCH3	4	178–179	C25H20O6
D31	6-OCH3	‐Cl	4	202–203	C24H17ClO5
D32	6-OCH3	‐NO2	4	226–227	C24H17NO7
D33	5-Cl	‐H	3	158–160	C23H15ClO4
D34	5-Cl	‐OCH3	3	205–207	C24H17ClO5
D35	5-Cl	‐Cl	3	199–200	C23H14Cl2O4
D36	5-Cl	‐H	4	214–216	C23H15ClO4
D37	5-Cl	‐OCH3	4	196–198	C24H17ClO5
D38	5-Cl	‐Cl	4	202–204	C23H14Cl2O4

Scheme 1. The synthesis of the benzofuran-3-one derivatives (A1–A4). Reactants/reagents and reaction conditions. a: (CH₃CO)₂O, reflux, 30 min; b: AlCl₃, 160–170 °C; c: (CH₃CO)₂O, 50–100 °C, 3–4 h; d: Br₂, HBr, diethyl ether or acetic acid; e: 10% HCl, reflux; f: CH₃COONa, EtOH, reflux.

Scheme 2. The synthesis of 6-methoxybenzofuranone (B). Reactants/reagents and reaction conditions. a: (CH₃)₂SO₄, NaOH, acetone, reflux, 4 h; b: AlCl₃, CS₂, dichloromethane, reflux, 30 min; c: CH₃COONa, EtOH, reflux.

Scheme 3. The synthesis of the final compounds (D1–D38). Reactants/reagents and reaction conditions. a: n-butanol/isobutanol, catalytic HCl, reflux, 1 h; b: acetone, K₂CO₃, reflux, 6 h.

Table 3. Sixty human tumor cell lines’ anti-cancer screening data at single dose assay as percent cell growth promotion of selected compounds.

Com	NSCLC	CC	BC	OC	L	RC	M	PC	CNSC	Mean
D-2	94.50	108.37	124.84	105.53	81.24	83.22	115.04	111.98	107.64	102.25
D-3	95.50	112.32	92.64	98.69	77.72	93.86	106.45	109.78	93.22	97.16
D-5	88.83	103.21	82.68	100.07	74.30	100.28	99.02	98.90	109.49	94.76
D-8	91.01	103.28	91.17	100.10	91.10	85.04	96.47	108.69	108.71	95.76
D-9	102.86	103.02	101.92	103.84	95.51	101.78	103.90	108.37	135.51	105.83
D-10	102.20	124.04	116.29	129.25	101.45	100.06	102.47	109.20	114.76	113.99
D-14	87.21	101.61	94.51	97.39	113.88	98.59	92.88	107.45	96.06	97.28
D-17	91.82	98.69	91.41	104.45	72.27	97.85	90.17	230.58	97.49	97.76
D-23	90.93	87.06	80.34	101.09	72.06	95.71	103.25	110.97	113.84	95.03
D-27	93.94	96.15	93.85	94.13	92.49	96.67	99.96	97.86	84.96	94.47
D-28	99.40	113.57	135.62	105.58	86.41	96.76	113.30	107.18	116.13	108.32
D-30	99.58	111.34	100.96	95.91	82.68	112.45	103.37	113.69	101.56	102.09
D-32	98.87	106.82	104.76	100.76	89.24	98.86	103.19	122.53	99.78	101.21
D-37	86.58	89.17	85.26	85.01	49.47	101.78	89.21	107.41	94.49	86.23

NSCLC, non-small cell lung cancer; CC, colon cancer; BC, breast cancer; OC, ovarian cancer; L, leukemia; RC, renal cancer; M, melanoma; PC, prostate cancer; CNSC, central nervous system cancer.

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