Synthesis and biological evaluation of certain 3-substituted benzylideneamino-2-(4-nitrophenyl)quinazolin-4(3H)-one derivatives

Figures & data

Scheme 1. Synthesis of the targeted 3-substituted benzylideneamino-2-(4-nitrophenyl)quinazolin-4(3H)-one derivatives 6–16.

Table 1. Curative anti-ulcerative colitis effect of compounds 6–16 on acetic acid-induced colitis in rats.

Groups	Dose (mg/kg)	Score	Ulcer area (mm^2)	Ulcer index	Wt/l	% Protection
Normal control	0	0	0	0	0.41 ± 0.03	0
Control colitis	0	3.30 ± 0.52	42.20 ± 1.47	45.50 ± 1.05	1.04 ± 0.09	0
Dexamethasone	0.01	1.80 ± 1.17	9.70 ± 1.03	11.50 ± 1.07	0.5* ± 0.08	75.30
6	50	3.00 ± 0.90	31.75 ± 1.85	33.75 ± 1.60	0.99 ± 0.09	25.82
7	50	2.00 ± 0.89	26.30* ± 1.48	28.33* ± 1.16	0.88* ± 0.09	37.74
8	50	2.33 ± 0.52	24.20* ± 1.48	26.80* ± 1.19	0.80* ± 0.08	41.1
9	50	3.00 ± 0.00	30.70 ± 1.57	33.70 ± 1.57	0.94 ± 0.10	25.93
10	50	2.80 ± 0.75	27.50 ± 1.09	30.30* ± 1.74	0.89 ± 0.07	33.41
11	50	2.30 ± 0.52	20.30* ± 2.85	22.70* ± 1.26	0.86* ± 0.07	50.10
12	50	2.70 ± 0.82	15.50* ± 1.26	18.20* ± 1.57	0.78* ± 0.10	60.00
13	50	1.50 ± 0.55	9.50* ± 1.51	11.00* ± 1.74	0.76* ± 0.14	75.82
14	50	1.30 ± 0.52	7.83* ± 1.94	9.20* ± 1.44	0.67* ± 0.12	79.78
15	50	1.80 ± 0.98	19.67* ± 1.75	21.50* ± 1.71	0.71* ± 0.14	52.75
16	50	3.00 ± 0.89	28.70 ± 1.85	32.00 ± 1.60	0.96 ± 0.09	29.67

Groups of six received the investigated compounds, standard and vehicle orally for five successive days after 1 h of ulcerative colitis induced by acetic acid. Two days later, animals were sacrificed, colonic segments were excised, opened and were used for macroscopic scoring. All values were expressed as mean ± SD.

*Significantly different from control colitis at p < 0.05.

Figure 1. Inhibition of sPLA2 activity.

Table 2. Inhibition data of compounds 6–16 against sPLA2 (DrG-IB and hG-IIA) activity.

	sPLA2 inhibitory activity (%)
Compounds	DrG-IB	hG-IIA
6	1.04 ± 2.79	15.56 ± 3.10
7	3.67 ± 1.53	24.67 ± 4.51
8	10.00 ± 2.00	47.33 ± 4.04
9	1.67 ± 2.89	18.33 ± 4.16
10	11.67 ± 3.52	52.00 ± 2.64
11	14.60 ± 2.52	69.33 ± 4.04
12	10.00 ± 3.00	37.33 ± 3.51
13	4.67 ± 0.58	52.00 ± 3.60
14	9.00 ± 1.73	45.00 ± 1.00
15	7.33 ± 1.53	37.67 ± 2.08
16	8.33 ± 1.15	30.00 ± 2.00

Figure 2. Inhibition of protease activity.

Table 3. Inhibition data of compounds 6–16 against protease activity.

Compounds	Protease inhibitory activity (%)
6	23.00 ± 4.00
7	41.33 ± 3.21
8	55.33 ± 4.50
9	28.00 ± 3.60
10	56.33 ± 3.21
11	71.33 ± 4.04
12	51.00 ± 2.64
13	57.33 ± 2.50
14	37.33 ± 3.21
15	31.67 ± 2.52
16	47.33 ± 2.52