Synthesis, inhibition of NO production and antiproliferative activities of some indole derivatives

Figures & data

Figure 1.  Structures of 6a and 6b.

Scheme 1.  Reagents: (i) ethyl acetoacetate (1 mol for 4a, excess for 4b); Indium(III)chloride; reflux 2h;(ii) but-2-ynoic acid; DCC; DMAP; CH₂Cl₂ /DMF (10:1); r.t. 2h; (iii) PtCl₄; 1,4-dioxane/1,2-dichloroethane (1:1); reflux 4h.

Scheme 2.  Reagents: (i) NaH, CH₃I, DMF, 25°C; (ii) pyiridine hydrochloride; 3h reflux.

Figure 2.  Percentage inhibition of NO production in LPS-induced RAW 264.7 macrophages for compounds 5a and 5b.

Figure 3.  Percentage inhibition of NO production in LPS induced RAW 264.7 macrophages for compounds 6a, 4a and 4b.

Table I.  IC₅₀ values of inhibition of NO production in LPS-induced RAW 264.7 macrophages for compounds.

Compds	IC50, μM^a
4a	83.5 ± 2.3**
4b	38.9 ± 1.1**
5a	1.1 ± 0.1**
5b	2.3 ± 0.1**
6a	43.7 ± 1.1**
6b	>100
Indomethacin^b	147.5 ± 1.2

^aValues are means of three experiments, standard deviation is given in parentheses.

^bIndomethacin was used as positive control. **p < 0.01.

Figure 4. Percentage inhibition on DPPH radical of compounds 4a, 4b and 5a.

Table II.  Radical scavenging activity of analyzed compounds.

Comps	IC50μM^a
4a	75. 0 ± 0.9**
4b	712.1 ± 1.3**
5a	802.2 ± 3.1**
5b	>1000
6a	>1000
6b	>1000

^aValues are means of three experiments, standard deviation is given in parentheses. ** p < 0.01. Ascorbic acid (2 μg/mL) was used as positive control.

Table III.  Cytotoxic activities against human tumor cell lines of compounds.

IC50 μM^a
Comps	COR-L23	A549	C32	A375
4a	>50	>50	>50	>50
4b	39.3 ± 1.3**	>50	>50	40.4 ± 1.4**
5a	38.9 ± 1.3**	>50	11.8 ± 0.5**	>50
5b	>50	>50	21.8 ± 0.9**	>50
6a	>50	>50	>50	>50
6b	>50	>50	>50	>50

^aValues are means of three experiments, standard deviation is given in parentheses. **p < 0.01. COR-L23: large lung carcinoma; A549: alveolar basal epithelial carcinoma; C32: amelanotic melanoma; A375: melanoma. Vinblastine (2 μg/mL) was used as positive control.