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Preparation of derivatives of ibuprofen and pre-clinical toxicity tests with single dose (acute) and repeated doses in mice

Grant number: 11/18583-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2012
Effective date (End): January 31, 2014
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Chung Man Chin
Grantee:Carla Maria Ribeiro Ferreira
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Inflammation is essentially a protective response tissue whose function is to protect and rid the body of microrganisms and toxins that promote cell damage. The inflammatory response generates the appearance of the four cardinal signs of pain, swelling, heat, redness and also can occur the loss of tissue or organ function. The anti-inflammatory drugs (NSAIDs)promote its activity by altering the activity of prostaglandins (PGs) by inhibiting the constitutive and induced isoforms of cyclooxygenases (COX1)and (COX2), respectivily. The nonselective inhibition (for classical NSAIDs) cause serious adverse reactions in patients by use for an extended period, such as gastrointestinal reactions. Selective NSAIDs (selective COX2 inhibitors), were also toxic, promoting cardiovascular changes. In this sense, the planning of new compounds with anti-inflammatory activity and devoid of toxicity is still a challenge for medicinal chemistry and pharmaceutics. Two derivatives of ibuprofen (NSAIDs) were obtained in Lapdesf demonstrating anti-inflammatory activity in models of acute inflammation (paw edema) and chronic (colitis), devoid of gastroulceration. Given these results the present study aims at the preparation of compounds and preclinical studies of toxicity in single dose (acute) and repeated doses in mice. (AU)