A New Class of Ibuprofen Derivatives with Reduced Gastrotoxicity

Abstract

A new series of nonsteroidal antiinflammatory drugs (NSAIDs) obtained by linking ibuprofen to selected furoxan moieties and to related furazans were synthesized and tested for their antiinflammatory, antiaggregatory, and ulcerogenic properties. All the derivatives are endowed with antiinflammatory activity comparable to that of ibuprofen, but, unlike this drug, they display reduced acute gastrotoxicity. The masking of the ibuprofen-free carboxylic group seems to be principally at the basis of this reduced topical irritant action. The two furoxan derivatives 8 and 9 also trigger potent antiaggregatory effects, principally as a consequence of their NO-donor ability.

Synthesis and investigation of anti-inflammatory activity and gastric ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives

“…The NO-donating oximes 13a and 13b were found to release fewer amount of NO compared to the previous nitrate esters 9a-d reaching their maximum after 5 h. The last group of nitrate esters 11a-c were found to release a moderate amount of NO reaching their maximum after 3 h and then begin to decrease gradually in the fourth hour. This may be attributed to the electron donating properties of the methyl group in the propionic acid spacer present in compounds 11a-c which decrease the dissociation of the nitrite group giving lower amount of NO compared to the acetic acid spacer present in compounds 9a-d. On the other hand there is no release of NO at pH 1 and this may support the fact that NO-donating moieties (nitrates and oximes) are weakly hydrolyzed in the gastric lumen and this confirms that the suggested gastroprotective action of NO is mediated systemically [35,36].…”

COX-2/5-LOX Dual Acting Anti-Inflammatory Drugs in Cancer Chemotherapy

“…So, the concept of hybrid molecules has been applied to the rational design of drugs in the structure of which the pharmacophoric elements of each target are separated by a linker or in which the pharmacophores are fused. This two technics have provided new agents useful in the treatment of various pathologies including cardiovascular diseases [137][138][139][140][141], pain [142], inflammation [143][144][145][146][147][148][149][150][151] and, for a long time, the hybrid molecule paradigm has been reported in our laboratory for the design of new efficient anti-cancer drugs [151][152][153][154][155].…”

Design and Evaluation of Primaquine-Artemisinin Hybrids as a Multistage Antimalarial Strategy

“…Hybrid (or bifunctional ligand) compounds, where two pharmacophores are combined in a single molecule, can be considered an extension of the concept of drug combinations in which the challenges of ensuring compliance with complex regimens or coformulating different compounds into a single tablet can be avoided. Hybrid molecules have been designed for use in various therapeutic areas, such as inflammation (6,16), allergy (2), and depression (20). Typically, two pharmacophores are conjugated through a linker unit, creating a single chemical entity that is able to modulate multiple targets.…”