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Diclofenac 1,3,4-Oxadiazole Derivatives; Biology-Oriented Drug Synthesis (BIODS) in Search of Better Non-Steroidal, Non-Acid Antiinflammatory Agents NEWS RELEASE: 12-01-2019

The article by Khalid Mohammed Khan and colleagues is published in Medicinal Chemistry, Volume 14, Issue 7, 2018

Inflammation in the body occurs due to the cellular response of the immune system to damaged or injured tissues. The major symptoms of inflammation include increased blood flow, cellular influx, edema, elevated cellular metabolism, reactive oxygen species (ROS) nitric oxide (NO) and vasodilation. Dysregulation of this normally protective mechanism can cause serious illnesses including ulcerative colitis, Crohn's disease, rheumatoid arthritis, osteoarthritis, sepsis, and chronic pulmonary inflammation.

Researchers at the International Center for Chemical and Biological Sciences, University of Karachi, in collaboration with PCSIR Laboratories Complex performed synthetic transformations on diclofenac in search of better non-steroidal antiinflammatory drugs (NSAIDs), non-acidic, antiinflammatory agents. For this purpose, diclofenac derivatives (2-20) were synthesized from diclofenac (1). All derivatives (2-20) and parent diclofenac (1) were evaluated for their antiinflammatory effect using different parameters including suppression of intracellular reactive oxygen species (ROS), produced by whole blood phagocytes, produced by neutrophils, and inhibition of nitric oxide (NO) production from J774.2 macrophages. The most active compound also evaluated for cytotoxicity activity on NIH-3T3 cells. Compounds 1-4 in the study have been documented in previous studies while the subsequent compounds represent new derivatives.

The researchers found five bioactive derivatives. Compound 5 (2-(5-(2-(2,6-Dichlorophenylamino)benzyl)-2-thioxo-1,3,4-oxadiazol-3(2H)-yl)-1-phenylethanone) was found to be the most potent inhibitor of ROS and NO compared to parent diclofenac 1 and standard drugs ibuprofen and L-NMMA, respectively. The most active compounds 1, 4, 5, 11 and 20 were found to be non-toxic on NIH-3T3 cells. Compound 4, 5, and 20 also showed good antiinflammatory potential, compound 11 and 16 showed moderate and low level of inhibition, respectively. Therefore, there is some potential to improve existing anti-inflammatory medications through synthesizing and testing new derivatives.

The article can be obtained from the following link:

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