21653-20-3Relevant articles and documents
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Hach,V.
, p. 1616 - 1623 (1977)
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Synthesis and evaluation of apoptotic induction of human cancer cells by ester derivatives of thujone
Castner, Emily,Dickson, Matthew,Mykytyn, Anna,Seeram, Navindra P.,Henry, Geneive E.,Vivekanand, Pavithra
, p. 268 - 280 (2019/12/09)
Thujone (1), thujol (2), and aromatic thujol esters (3–9) were evaluated for their ability to induce cell death in human cervical (HeLa), melanoma (A375), and colon (HCT-116) cancer cell lines, using etoposide as a positive control. The compounds showed dose-dependent activity at concentrations ranging from 50–400 μg/mL. Etoposide exhibited an IC50 value of 116 μg/mL in HeLa cells, and α-thujone, α/β-thujone (7:1), and thujol showed comparable activity with IC50 values of 191, 198, and 136 μg/mL, respectively. All seven ester derivatives were cytotoxic to HeLa and HCT-116 cells, while a subset was cytotoxic to A375 cells. In HeLa cells, t-cinnamate (4), t-isonicotinate (5), t-nicotinate (6), and t-furoate (8) were more potent than either α-thujone or α/β-thujone. Similarly, t-furoate (8) was more potent than thujone in A375 cells, and t-isonicotinate (5) and t-nicotinate (6) were more potent against HCT-116 cells. Based on cell morphology, PARP cleavage and an increase in the caspase-3/7 levels, the esters exert their cytotoxic effects by induction of apoptosis.
Substrate flexibility and reaction specificity of tropinone reductase-like short-chain dehydrogenases
Reinhardt, Nicole,Fischer, Juliane,Coppi, Ralph,Blum, Elke,Brandt, Wolfgang,Draeger, Birgit
, p. 37 - 49 (2014/03/21)
Annotations of protein or gene sequences from large scale sequencing projects are based on protein size, characteristic binding motifs, and conserved catalytic amino acids, but biochemical functions are often uncertain. In the large family of short-chain dehydrogenases/reductases (SDRs), functional predictions often fail. Putative tropinone reductases, named tropinone reductase-like (TRL), are SDRs annotated in many genomes of organisms that do not contain tropane alkaloids. SDRs in vitro often accept several substrates complicating functional assignments. Cochlearia officinalis, a Brassicaceae, contains tropane alkaloids, in contrast to the closely related Arabidopsis thaliana. TRLs from Arabidopsis and the tropinone reductase isolated from Cochlearia (CoTR) were investigated for their catalytic capacity. In contrast to CoTR, none of the Arabidopsis TRLs reduced tropinone in vitro. NAD(H) and NADP(H) preferences were relaxed in two TRLs, and protein homology models revealed flexibility of amino acid residues in the active site allowing binding of both cofactors. TRLs reduced various carbonyl compounds, among them terpene ketones. The reduction was stereospecific for most of TRLs investigated, and the corresponding terpene alcohol oxidation was stereoselective. Carbonyl compounds that were identified to serve as substrates were applied for modeling pharmacophores of each TRL. A database of commercially available compounds was screened using the pharmacophores. Compounds identified as potential substrates were confirmed by turnover in vitro. Thus pharmacophores may contribute to better predictability of biochemical functions of SDR enzymes.
