The reported pharmacological activities of acetylenic and phthalimide groups promoted our interest to
synthesize a novel series of N-[4-(t-amino-yl)-but-2-yn-1-yl] isoindoline-1,3-diones as anti-inflammatory compounds.
The aim of this research is to investigate the selectivity of two compounds, ZM4 and ZM5, on inhibiting cyclooxygenase
(COX) in vitro and in silico as well as reducing carrageenan-induced edema in rats. Oral administration of 5-20 mg/kg
ZM4 and ZM5 reduced significantly carrageenan-induced edema in dose-and time dependent manner. Furthermore, the
IC50 values induced by ZM4 and ZM5 were in the range of 3.0-3.6 M for COX1 and COX 2 but were higher than those
induced by Diclofenac and Celecoxib, respectively. Docking of ZM4 and ZM5 in both COX enzymes, on the other hand,
exhibited the conventional binding modes that are usually adopted by different non-steroidal anti-inflammatory drugs
(NSAIDs). Furthermore, ZM4 and ZM5 bind to COX enzymes as strongly as Flurbiprofen and Celecoxib. In conclusion,
aminoacetylenic isoindoline 1, 3-dione compounds have shown anti-inflammatory activity by inhibiting COX-1 and
COX-2 enzymes. Interestingly, the best hits showed inhibition at low micromolar levels although they are not selective at
this stage. Further research will be conducted to improve both selectivity and potency.
Keywords: Aminoacetylenic isoindoline, COX inhibtors, docking, anti-inflammatory compounds, ZM4, ZM5, non-steroidal anti-inflammatory drugs, Celecoxib, Aminoacetylenic Isoindoline 1, 3-Diones, cyclooxygenase.
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