Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease
Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2007-04, Vol.17 (7), p.1897-1902 |
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| container_end_page | 1902 |
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| container_issue | 7 |
| container_start_page | 1897 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 17 |
| creator | DHANESHWAR, Suneela S GAIROLA, Neha KANDPAL, Mini BHATT, Lokesh VADNERKAR, Gaurav KADAM, S. S |
| description | Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid. |
| doi_str_mv | 10.1016/j.bmcl.2007.01.031 |
| format | Article |
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Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2007.01.031</identifier><identifier>PMID: 17280832</identifier><language>eng</language><publisher>Oxford: Elsevier</publisher><subject>Animals ; Biological and medical sciences ; Chemistry, Pharmaceutical - methods ; Colon - pathology ; Digestive system ; Drug Delivery Systems ; Drug Design ; Hydrochloric Acid - chemistry ; Inflammatory Bowel Diseases - drug therapy ; Kinetics ; Medical sciences ; Mesalamine - chemical synthesis ; Mesalamine - pharmacology ; Models, Chemical ; Molecular Conformation ; Pharmacology. Drug treatments ; Phenylalanine - chemical synthesis ; Phenylalanine - pharmacology ; Prodrugs - pharmacology ; Rats ; Sulfasalazine - chemistry</subject><ispartof>Bioorganic & medicinal chemistry letters, 2007-04, Vol.17 (7), p.1897-1902</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18632118$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17280832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DHANESHWAR, Suneela S</creatorcontrib><creatorcontrib>GAIROLA, Neha</creatorcontrib><creatorcontrib>KANDPAL, Mini</creatorcontrib><creatorcontrib>BHATT, Lokesh</creatorcontrib><creatorcontrib>VADNERKAR, Gaurav</creatorcontrib><creatorcontrib>KADAM, S. S</creatorcontrib><title>Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>Colon - pathology</subject><subject>Digestive system</subject><subject>Drug Delivery Systems</subject><subject>Drug Design</subject><subject>Hydrochloric Acid - chemistry</subject><subject>Inflammatory Bowel Diseases - drug therapy</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Mesalamine - chemical synthesis</subject><subject>Mesalamine - pharmacology</subject><subject>Models, Chemical</subject><subject>Molecular Conformation</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenylalanine - chemical synthesis</subject><subject>Phenylalanine - pharmacology</subject><subject>Prodrugs - pharmacology</subject><subject>Rats</subject><subject>Sulfasalazine - chemistry</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1u1TAQhS0EoreFF2CBvIFVE-zE8c8SlV-pEgtAYnc1sce9Lo4d4qRVeDYejly4CGlGozn6dEZnCHnGWc0Zl69u636wsW4YUzXjNWv5A7LjQoqqFax7SHbMSFZpI76dkfNSbhnjggnxmJxx1Wim22ZHfn1e03zAEsol_R4SzsHSMi8uYKGQHB0PMA1gc8w3wUKkeAdxgTnkRLOnwzIvmwg_Mx2n7Kbl5qh2FQwh5QIx2HVrCjY4eh_mA31TjQdMa4QIabtGfZ7o0TzRMqINfoP_uDiM4Q6nlYa0lY8wDDDnbe_zPUbqQkEo-IQ88hALPj3NC_L13dsvVx-q60_vP169vq5G3om5MlI5o7jkvfG-Qw1WK8uMc6CNbJT22gmGGnUvlZfWKqUtgrW9FdIYz9sL8vKv7xbyx4Jl3g-hWIxbCMxL2SvWdMKwI_j8BC79gG4_TmGAad3_-_cGvDgBULZ3-gmSDeU_p2XbcK7b310-lmA</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>DHANESHWAR, Suneela S</creator><creator>GAIROLA, Neha</creator><creator>KANDPAL, Mini</creator><creator>BHATT, Lokesh</creator><creator>VADNERKAR, Gaurav</creator><creator>KADAM, S. 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S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>17</volume><issue>7</issue><spage>1897</spage><epage>1902</epage><pages>1897-1902</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.</abstract><cop>Oxford</cop><pub>Elsevier</pub><pmid>17280832</pmid><doi>10.1016/j.bmcl.2007.01.031</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Biological and medical sciences Chemistry, Pharmaceutical - methods Colon - pathology Digestive system Drug Delivery Systems Drug Design Hydrochloric Acid - chemistry Inflammatory Bowel Diseases - drug therapy Kinetics Medical sciences Mesalamine - chemical synthesis Mesalamine - pharmacology Models, Chemical Molecular Conformation Pharmacology. Drug treatments Phenylalanine - chemical synthesis Phenylalanine - pharmacology Prodrugs - pharmacology Rats Sulfasalazine - chemistry |
| title | Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease |
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