The Pharmacological effects of novel 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamide derivatives on plasma lipid profile of Triton-WR-1339-induced Wistar rats

Figures & data

Scheme 1.  Synthesis route for the preparation of compounds (3c–3g). Reagents and conditions: (a) dichloromethane, reflux 6h; (b) NaH, N,N-dimethylformamide, reflux 24h

Figure 1.  Effect of Triton-WR-1339 on lipid profile after (a) 12 h and (b) 24 h. Values are means ± SD from six animals in each group. NCG, control group; HCG, hyperlipidemic control group; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. HCG is compared to NCG. ^*p < 0.0001.

Figure 2.  Dose-response study of the tested compounds. 3c, 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-1-yl)-1H-indole-2-carboxamide treated group; 3d, N-(1-chloro-9,10-dihydro-9,10-dioxoanthracen-5-yl)-5-fluoro-1H-indole-2-carboxamide treated group; 3e, 5-fluoro-N-(9,10-dihydro-1-hydroxy-9,10-dioxoanthracen-4-yl)-1H-indole-2-carboxamide; 3f, N-(1-bromo-9,10-dihydro-3-methyl-9,10-dioxoanthracen-4-yl)-5-fluoro-1H-indole-2-carboxamide; 3g, 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-3-yl)-1H-indole-2-carboxamide.

Table 1.  Effect of compounds 3c, 3d, 3e, 3f, 3g and bezafibrate on plasma lipid levels in Triton WR-1339-induced hyperlipidemic rats after 12 h and 24 h.

Lipid profile	TC (mg/dL)	TG (mg/dL)	HDL-C (mg/dL)	LDL-C (mg/dl)
12 h
HCG	174.00 ± 4.0	1899.00 ± 7.0	12.60 ± 1.0	74.00 ± 2.1
3c	116.00 ± 3.0^**	515.00 ± 4.0^**	17.60 ± 0.5^**	44.90 ± 4.0^**
3d	109.00 ± 5.0^**	491.00 ± 22.0^**	18.70 ± 1.0^**	43.80 ± 1.0^**
3e	94.00 ± 5.0^**	260.00 ± 10.0^**	31.20 ± 1.6^**	36.90 ± 0.8^**
3f	105.00 ± 5.0^**	472.00 ± 7.0^**	17.10 ± 0.3^**	46.20 ± 1.0^**
3g	140.00 ± 2.2^**	372.00 ± 9.0^**	27.00 ± 0.8^**	30.80 ± 0.8^**
BF	179.00 ± 3.0	225.00 ± 8.0^**	40.20 ± 1.5^**	73.70 ± 3.7
24 h
HCG	378.00 ± 10.0	1644.00 ± 25.0	15.40 ± 0.9	68.00 ± 1.6
3c	374.00 ± 6.0	1291.00 ± 8.0^**	16.50 ± 0.6^**	65.50 ± 1.0
3d	367.00 ± 2.0	1252.00 ± 10.0^**	18.40 ± 0.9^*	66.70 ± 1.7
3e	363.00 ± 5.0^**	1094.00 ± 9.0^**	21.30 ± 1.0^**	64.20 ± 1.5^**
3f	369.00 ± 5.0	1258.00 ± 13.0^**	17.10 ± 0.7^**	64.90 ± 3.7
3g	344.00 ± 5.0^**	1100.00 ± 11.0^**	19.60 ± 0.6^*	55.10 ± 0.9^**
BF	100.00 ± 6.8	787.00 ± 8.0^**	24.20 ± 1.9^*	70.00 ± 0.2

Values are means ± SD from six animals in each group. Compounds 3c, 3d, 3e, 3f, 3g and BF are compared with HCG.

HCG, hyperlipidemic control group; 3c, 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-1-yl)-1H-indole-2-carboxamide treated group; 3d, N-(1-chloro-9,10-dihydro-9,10-dioxoanthracen-5-yl)-5-fluoro-1H-indole-2-carboxamide treated group; 3e, 5-fluoro-N-(9,10-dihydro-1-hydroxy-9,10-dioxoanthracen-4-yl)-1H-indole-2-carboxamide; 3f, N-(1-bromo-9,10-dihydro-3-methyl-9,10-dioxoanthracen-4-yl)-5-fluoro-1H-indole-2-carboxamide; 3g, 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-3-yl)-1H-indole-2-carboxamide; BF, bezafibrate treated group; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

*p < 0.05; ^**p < 0.0001.