PMID: 8974453Sep 1, 1995Paper

Synthesis, binding affinity, and cross-linking of monodentate photoactive phenothiazines to calmodulin

Bioconjugate Chemistry
M GolinskiD S Watt

Abstract

Various photoactive phenothiazines were synthesized that possessed a 2-azido, 3-azido, 2-benzoyl, or 1,3,4-trifluoro-2-azido functionality in combination with various modifications of the N-alkyl side chain. These phenothiazines were evaluated for their ability to inhibit the calmodulin-mediated activation of phosphodiesterase (PDE). All were active in inhibiting the action of calmodulin (CaM), but those possessing either a 3-azido and a 4-(4-methyl-1-piperazinyl)butyl side chain or a 2-benzoyl group and 3-(dimethylamino)propyl side chain proved to be most active (I50 = 14 +/- 3 microM and 7 +/- 1 microM, respectively) when compared to the known inhibitor, chlorpromazine (CPZ, I50 = 30 microM). Calmodulin was photolabeled with ca. 35% efficiency in a light- and calcium-dependent fashion using a radiolabeled analog, 3-azido-10-(4-(4-[14C]methyl-1-piperazinyl)butyl)phenothiazine, of one of these compounds. Competition studies using this radiolabeled analog and CPZ were consistent with binding to one or both of the hydrophobic binding pockets of CaM.

Citations

Feb 1, 1997·Photochemistry and Photobiology·G D PrestwichA Chaudhary
May 23, 2018·International Journal of Molecular Sciences·Kjell De VrieseSteffen Vanneste
Mar 16, 2013·Chemistry & Biodiversity·Martín González-AndradeRachel Mata

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