Design, synthesis and anti-ulcerogenic effect of some of furo-salicylic acid derivatives on acetic acid-induced ulcerative colitis.
Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present work describes design and synthesis of 3-aminofurosalicylic acid 4, azo-conjugates with aniline 2a, 4-ASA 2b or sulphapyridine 2c as well as N-arylsulphonamido 5, chlorosulphonyl 6, aminosulphonyl 7 and N-arylaminosulphonyl derivatives 8 (positional isosters of 5). All the synthesized compounds were evaluated for their anti-ulcerogenic effect on acetic acid-induced ulcerative colitis in rats. It was noticed that oral treatment with sulphasalazine (a reference drug) and the tested compounds 2a, 2c, 4 and 5c in equimolar doses significantly reduced the intensity of lesion score, ulcer area, ulcer index and wet weight/length ratio compared to the control group. On the other hand, compounds 2b, 5a, 5b and 7 had a lower anti-ulcerogenic efficacy. Also, the antimicrobial activity of the synthesized compounds was screened in vitro using the agar diffusion assay technique. In addition, docking of the tested compounds into cycloxygenase II using molecular operating environment (MOE) was performed in order to rationalize the obtained biological results and their mechanism of action.
Hassan
Ghaneya S
GS
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-Kasr El-Aini Street, Cairo 11562 Cairo, Egypt. ghanmoom@yahoo.com
Soliman
Gamal A
GA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001419:Bacteria / Q000187:drug effects; D001572:Benzofurans / Q000737:chemistry*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D007928:Lethal Dose 50; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D020156:Salicylic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013270:Stomach / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D052246:Cyclooxygenase 2 Inhibitors; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D020156:Salicylic Acid