Analyses of synthetic N-Acyl Dopamine derivatives reveal differential structural requirements for their anti-inflammatory and transient receptor potential channel of the vanilloid receptor subfamily subtype 1 (TRPV1) activating propertiesPallavi, P., Pretze, M., Caballero, J., Li, Y., Hofmann, B. B., Stamellou, E., Klotz, S., Wängler, C., Wängler, B., Loesel, R., Roth, S., Theisinger, B., Moerz, H., Binzen, U., Greffrath, W., Treede, R-D., Harmsen, M. C., Krämer, B. K., Hafner, M., Yard, B. A. & Kälsch, A-I., 2018, In : Journal of Medicinal Chemistry. 61, 7, p. 3126-3137 12 p.
Research output: Contribution to journal › Article › Academic › peer-review
We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) activation and inhibition of inflammation. The efficacy of NOD to activate TRPV1 was significantly higher compared to variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted (N-octanoyl tyramine) or the ester functionality consisted of a bulky fatty acid (N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its efficacy which further increased by interchanging the carbonyl and amide groups (ΔNODR). With the exception of ΔNOD, the presence of an intact catechol structure was obligatory for inhibition of VCAM-1 and induction of HO-1 expression. Since TRPV1 activation and inhibition of inflammation by N-acyl dopamines require different structural entities, our findings provide a framework for the rational design of TRPV1 agonists with improved anti-inflammatory properties.
|Number of pages||12|
|Journal||Journal of Medicinal Chemistry|
|Early online date||15-Mar-2018|
|Publication status||Published - 2018|
- Journal Article, REGION, PAIN, N-OCTANOYL-DOPAMINE, TRPV1 ION-CHANNEL, ANALGESIC AGENTS, AGONIST ACTIVITY, CAPSAICIN, ACTIVATION, HYPERALGESIA, ANALOGS