Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis

Figures & data

Figure 1 Chemical structures of compounds 1, 2, and 3.

Figure 2 Synthesis of compound 1.

Figure 3 Chemical structure of compound 4.

Figure 4 Synthesis of compound 2.

Table 1 Inflammation scores of synthesized prodrug-treated rat colons, by histopathological examination

Group-Rat #	Mucosal ulceration	Wall thickness	Transmucosal inflammation	Overall score of inflammation
A1	3	3	4	3
A2	4	4	5	4
A3	4	4	5	4
A4	–	–	–	Died
A5	3	4	4	3
A6	4	4	4	4
B1	1	1	1	1
B2	1	1	1	1
B3	2	3	1	2
B4	2	3	3	3
B5	1	1	1	1
B6	1	1	1	1
C1	1	1	1	1
C2	3	2	1	2
C3	3	1	1	2
C4	3	1	1	2
C5	3	2	1	2
C6	3	2	1	2
D1	3	3	3	3
D2	3	1	1	2
D3	3	3	3	3
D4	1	1	1	1
D5	3	3	3	3
D6	3	3	1	2

Notes: Groups were: A was the negative control; B was treated with 5-ASA-treated; C was treated with compound 4; and D was treated with compound 1. The inflammation scores were: 1 = normal; 2 = very minimal; 3 = mild; 4 = moderate; and 5 = severe.

Figure 5 Representative histopathology pictures from rat colons treated with synthesized prodrugs: (A) a representative picture of group a (negative control) showing severe mucosal and transmural inflammation, in addition to increased wall thickness; (B) a representative picture of group B (treated with 5-ASA), shows that mucosal inflammation and ulceration were minimal and no increase in wall thickness was present; (C) a representative picture of group C (treated with compound 4) showing mucosal ulceration with no transmural inflammation or increase of wall thickness; and (D) a representative picture of group D (treated with compound 1) shows mucosal ulceration with no transmural inflammation and that wall thickness was minimally increased.

Notes: All pictures show staining with hematoxylin and eosin. Pictures A and C are at 40 × , pictures B and D are at 10×).