Synthesis and biological evaluation of asymmetric indole curcumin analogs as potential anti-inflammatory and antioxidant agents

Figures & data

Figure 1. Some reported asymmetrical curcumin analogs.

Scheme 1. Synthetic route of asymmetrical indole curcumin analogs: (a) NaOH, EtOH, 80 °C and (b) 40% NaOH, EtOH, RT.

Table 1. COX-2, trypsin and β-glucuronidase inhibitory activities (%) of AICAs (at 10 μM).

Compound	R	COX-2 (%)	Trypsin (%)	β-Glu (%)
5a	C6H5	12.00	3.2	42.56
5b	3-CF3C6H4	33.34	4.1	12.00
5c	3-CH3C6H4	34.38	11.75	58.95
5d	4-C(CH3)3C6H4	43.34	16.82	38.45
5e	4-F C6H4	83.33	22.62	67.80
5f	2-F C6H4	38.88	1.5	9.50
5g	3-CN C6H4	30.00	9.7	15.50
5h	4-MeOC6H4	82.50	25.08	64.12
5i	4-ClC6H4	48.25	20.64	52.91
5j	3-BrC6H4	32.40	12.50	35.22
ASA	–	35.10	88.34	ND
SA	–	ND	ND	26.20

The results summarized are the mean values of n = 2. ASA = acetyl salicylic acid, SA = salicylic acid, ND = not determined.

Table 2. TNF-α and IL-6 inhibitory activities and cytotoxicity of AICAs.

		% Inhibition at 10 μM
Compound	R	TNF-α	IL-6	Cytotoxicity
5a	C6H5	87	100	57
5b	3-CF3C6H4	88	100	62
5c	3-CH3C6H4	39	95	49
5d	4-C(CH3)3C6H4	28	93	45
5e	4-F C6H4	48	98	51
5f	2-F C6H4	51	87	45
5g	3-CN C6H4	59	71	63
5h	4-MeOC6H4	45	93	47
5i	4-ClC6H4	32	78	53
5j	3-BrC6H4	48	79	49
DMS (1 µM)	–	71	91	00
Curcumin	–	84	67	00

Results summarized are the mean values of n = 2. DMS = dexamethasone.

Table 3. DPPH radical scavenging and reducing activities (RA) of AICAs (at 10 μM).

Compound	R	DPPH (%)	RA (%)
5a	C6H5	41.92	32.45
5b	3-CF3C6H4	52.69	62.12
5c	3-CH3C6H4	45.96	78.68
5d	4-C(CH3)3C6H4	43.65	28.09
5e	4-F C6H4	44.23	35.34
5f	2-F C6H4	44.61	21.44
5g	3-CN C6H4	29.80	70.62
5h	4-MeOC6H4	45.78	38.26
5i	4-ClC6H4	41.89	33.45
5j	3-BrC6H4	43.18	71.82
GA	–	80.86	ND
AA	–	ND	52.93

The results summarized are the mean values of n = 2. GA = gallic acid,

AA = ascorbic acid, ND = not determined, RA = reducing activity.