Design, Synthesis and Hydrolysis Study of Gatifloxacin-NSAIDs as Mutual Prodrugs

摘要

Four different well-known non-steroidal anti-inflammatory drugs (naproxen, ketoprofen, diclofenac and ibuprofen) were linked to gatifloxacin anti-infective drug which possess anti-inflammatory activity, using chloroacetyl chloride as spacer, in order to synthesize a novel mutual prodrugs that give synergestic anti-inflammatory effect, in addition to temporary mask the carboxyl group of the non-steroidal drugs, which reduce the gastric ulceration and bleeding. The chemical structures of the synthesized compounds were confirmed and characterized using FT-IR spectroscopy, ~1H NMR spectroscopy, elemental microanalysis, melting points and Rf values, in vitro hydrolysis study of the synthesized mutual prodrugs was performed at different pHs (1.2 and 7.4), which reveal the chemical stability of these compounds inside the gastrointestinal tract. While their hydrolysis in 80 % human plasma, was revealed rapid conversion of the four synthesized prodrugs inside blood circulation to give the parent drug molecules, with about 40-55 % hydrolysis occur in the first hour.