1.Chemical modifications of cinchona alkaloids lead to enhanced inhibition of human butyrylcholinesterase.
Karlsson D, Fallarero A, Shinde P, Anju CP, Busygin I, Leino R, Mohan CG, Vuorela P. Nat Prod Commun. 2014 Apr;9(4):455-8.
Butyrylcholinesterase (BChE) inhibitors were identified from a collection containing cinchonine, cinchonidine and synthetic derivatives, and further characterized using cytotoxicity and molecular docking studies. The most active ones were: (10 triple bond)-10,11-dibromo-10,11-dihydrocinchonidine (11), a competitive inhibitor with Ki = 3.45 +/- 0.39 microM, and IC50 BChE = 9.83 +/- 0.30 microM/human (h)BChE = 34.47 +/- 4.63 and O-(trimethylsilyl)cinchonine (15), a mixed inhibitor with Kiuc = 1.73 +/- 0.46 microM and Kic = 0.85 +/- 0.26 microM, and IC50 BChE = 0.56 +/- 0.14 microM/hBChE = 0.24 +/- 0.04. In cytotoxicity experiments, > or = 80% of the cells remained viable when exposed to concentrations of up to 80 microM of both inhibitors in four different cell lines, including neurons. Due to the bulkier trimethylsilyl side group of 15, it covered the active site of hBChE better than 11 with an OH-group while not being able to fit into the active site gorge of hAChE, thus explaining the selectivity of 15 towards hBChE.
2.Exotic Protonated Species Produced by UV-Induced Photofragmentation of a Protonated Dimer: Metastable Protonated Cinchonidine.
Alata I1, Scuderi D2, Lepere V1, Steinmetz V2, Gobert F2, Thiao-Layel L2, Le Barbu-Debus K1, Zehnacker-Rentien A1. J Phys Chem A. 2015 Oct 1;119(39):10007-15. doi: 10.1021/acs.jpca.5b06506. Epub 2015 Sep 16.
A metastable protonated cinchona alkaloid was produced in the gas phase by UV-induced photodissociation (UVPD) of its protonated dimer in a Paul ion trap. The infrared multiple photon dissociation (IRMPD) spectrum of the molecular ion formed by UVPD was obtained and compared to DFT calculations to characterize its structure. The protonation site obtained thereby is not accessible by classical protonation ways. The protonated monomer directly formed in the ESI source or by collision-induced dissociation (CID) of the dimer undergoes protonation at the most basic alkaloid nitrogen. In contrast, protonation occurs at the quinoline aromatic ring nitrogen in the UVPD-formed monomer.
3.Combined use of [TBA][L-ASP] and hydroxypropyl-β-cyclodextrin as selectors for separation of Cinchona alkaloids by capillary electrophoresis.
Zhang Y1, Yu H2, Wu Y1, Zhao W1, Yang M1, Jing H3, Chen A4. Anal Biochem. 2014 Oct 1;462:13-8. doi: 10.1016/j.ab.2014.06.008. Epub 2014 Jun 20.
In this paper, a new capillary electrophoresis (CE) separation and detection method was developed for the chiral separation of the four major Cinchona alkaloids (quinine/quinidine and cinchonine/cinchonidine) using hydroxypropyl-β-cyclodextrin (HP-β-CD) and chiral ionic liquid ([TBA][L-ASP]) as selectors. Separation parameters such as buffer concentrations, pH, HP-β-CD and chiral ionic liquid concentrations, capillary temperature, and separation voltage were investigated. After optimization of separation conditions, baseline separation of the three analytes (cinchonidine, quinine, cinchonine) was achieved in fewer than 7 min in ammonium acetate background electrolyte (pH 5.0) with the addition of HP-β-CD in a concentration of 40 mM and [TBA][L-ASP] of 14 mM, while the baseline separation of cinchonine and quinidine was not obtained. Therefore, the first-order derivative electropherogram was applied for resolving overlapping peaks. Regression equations revealed a good linear relationship between peak areas in first-order derivative electropherograms and concentrations of the two diastereomer pairs.
4.Sensing of enantiomeric excess in chiral carboxylic acids.
Akdeniz A1, Mosca L, Minami T, Anzenbacher P Jr. Chem Commun (Camb). 2015 Apr 4;51(26):5770-3. doi: 10.1039/c5cc00376h.
Cinchona alkaloids (quinine, quinidine, cinchonine, cinchonidine) alkylated at N(1) with chloromethyl anthracene can serve as fluorescent sensors for chiral carboxylic acids. These cinchona ammonium salts are shown to bind chiral carboxylic acids while displaying an increase in fluorescence intensity that can be utilized in determination of enantiomeric excess (ee). Sensor arrays composed of four cinchona ammonium salts are used for quantitative analysis of ee in several non-steroidal anti-inflammatory drugs (NSAIDs), such as enantiomers of ibuprofen, ketoprofen, and naproxen.
