The endocannabinoid arachidonyl ethanolamide (AEA) and prostaglandins derived from it selectively induce apoptosis in tumorigenic cell lines due to overexpression of COX-2. It is likely that a novel J-series prostaglandin, 15-deoxy-Δ12,14-prostaglandin J2-ethanolamide (15dPGJ2-EA), is the cytotoxic mediator of AEA-induced apoptosis. Conjugation of a fluorescent group to prostaglandins of interest may be helpful in determining localization and pharmacokinetic properties needed for clinical development. The synthetic flexibility and bright luminescence of naphthalimides make them attractive probes for this purpose. Previous studies in our labs focused on identifying substituents on naphthalimide that cause minimal interference with intracellular drug localization and metabolism. Those studies indicated that a 4-morpholino naphthalimide would be a suitable probe for conjugation based on its lack of cytotoxicity. Unfortunately, we found that this probe renders AEA inactive, presumably by preventing its cyclization into prostaglandins. We hypothesize that conjugation of the 4-morpholino naphthalimide to an already-cyclized metabolite, such as 15dPGJ2-EA, will allow the drug to retain its activity.

Fluorescent derivatives of prostaglandins: Tools for studying anti-cancer activity

255th National Meeting (2018)

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