Synthesis and biological evaluation of new prodrugs of etodolac and tolfenamic acid with reduced ulcerogenic potential

A Novel Curcumin-Mycophenolic Acid Conjugate Inhibited Hyperproliferation of Tumor Necrosis Factor-Alpha-Induced Human Keratinocyte Cells

“…EDC was selected because the unreacted EDC can be easily removed from the reaction by partitioning with water due to its good water solubility [ 39 ]. Several organic solvents, including DCM and DMF ( N , N -dimethylformamide), are commonly used in the Steglich esterification method [ 37 , 38 , 40 , 41 ]. Due to the low solubility of curcumin in DCM, a large volume of DCM used to dissolve CUR resulted in a very diluting reaction mixture.…”

“…Our experiment used CUR (368.38 mg, 1 mmol) and MPA (320.34 mg, 1 mmol) to get the mutual prodrug of MPA-CUR as a monosubstitution. In this study, the Steglich esterification method, as shown in Figure 2, was used to synthesize the MPA-CUR ester prodrug [37,38]. Our experiment used an equimole of CUR and MPA to obtain the MPA-CUR conjugate as a monosubstitution.…”

Different consequences of the treatment of osteoarthritis in gastrointestinal comorbidity with exocrine pancreatic insufficiency

“…Much attention has been paid to the investigation of the development of side effects with the use of NSAIDs [19][20][21][22][23][24]. The main side effects after NSAIDs which have been covered in many studies [25][26][27][28][29][30][31][32] are gastrointestinal disorders (nausea, vomiting, abdominal pain, diarrhea, constipation, flatulence, dyspepsia, dry mouth, peptic ulcers, bleeding, perforated ulcers, anorexia, elevated liver enzymes, pancreatic damage, and hepatic damage) [33][34][35][36][37]; neurological disorders (sleep disorders, anxiety, headache, dizziness, hot flashes, and paresthesia); disorders of the cardiovascular system (increased blood pressure, palpitations, tachycardia, hypotension, and peripheral edema) [38][39][40]; allergic complications (bronchospasm, shortness of breath, skin rash, the Stevens-Johnson and Lyell syndromes, photosensitization, anaphylactic reactions, facial edema, and itching) [41,42]; disorders of the genitourinary system (nephritis or nephrotic syndrome, polyuria, menstrual disorders in women, and disorders of the prostate in men) [39]. Much attention is paid to the study of acid-dependent diseases of the gastrointestinal tract, which develop after NSAIDs use [43,44].…”

Tailored Functionalization of Natural Phenols to Improve Biological Activity

“…Promising results have also been achieved with the conjugation of nonsteroidal anti-inflammatory drugs (NSAIDs) to thymol, to prevent adverse gastrointestinal mucosal reactions, which are typical side effects related with long-term use of NSAIDs [ 137 , 138 , 139 , 140 ]. The formation of gastric ulceration related with NSAID therapy is usually due to the local generation of reactive oxygen species (ROS); thus, the introduction of antioxidant components in NSAIDs’ structure can limit such undesired effects.…”

“…The formation of gastric ulceration related with NSAID therapy is usually due to the local generation of reactive oxygen species (ROS); thus, the introduction of antioxidant components in NSAIDs’ structure can limit such undesired effects. Accordingly, thymol esterification product with indomethacin, etodolac and tolfenamic acid showed retention of pharmacological activity with respect to the parent drug and significant reduction in ulcerogenic side effects of the corresponding NSAID [ 137 ]. Similarly, thymol has been included in ketoprofen drug (2-(3-benzoylphenyl)propanoic acid), through a glycolic acid spacer ( Scheme 13 ) [ 139 ].…”