Synthesis and Spectroscopic and Structural Studies of Cross‐Conjugated Dienones Derived from Cyclic Ketones and Aromatic Aldehydes.

Вацадзе, С. З.; Manaenkova, M. A.; Sviridenkova, N. V.; Зык, Н. В.; Krut’ko, D. P.; Churakov, Andrei V.; Antipin, M. Yu.; Howard, Judith A. K.; Lang, Heinrich

doi:10.1002/chin.200716091

Cited by 2 publications

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“…High Resolution Mass Spectrometry (HRMS) (+ve ESI) calculated for C 20 H 21 N 3 ONa + : 342.1577 m/z, and [MNa + ] found 342.1567 m/z. Nuclear magnetic resonance spectroscopy character of molecule was consistent with literature values (33) (Fig. 1A,B).…”

Section: Methodssupporting

confidence: 90%

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

Megna

Carney

Depke

et al. 2017

Journal of Surgical Research

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BACKGROUND Curcumin has proven to be a potent antitumor agent in both preclinical and clinical models of colorectal cancer (CRC). It has also been identified as a ligand of the transcription factor known as the aryl hydrocarbon receptor (AHR). Our lab has identified the AHR as a mechanism which contributes to both tumorigenesis in a mouse model of inflammatory CRC as well an apoptotic target in vitro. Curcumin’s role as an AHR ligand may modulate its effects to induce colon cancer cell death, and this role may be enhanced via structural modification of the curcumin backbone. We sought to determine if the two piperidone analogs of curcumin, RL66 and RL118, exhibit more robust antitumor actions than their parent compound in the context of colorectal cancer in vitro. Moreover, to ascertain the ability of curcumin, RL66, and RL118 to activate the aryl hydrocarbon receptor and evaluate if this activation has any effect on CRC cell death. MATERIALS AND METHODS DLD1, HCT116, LS513, and RKO colon cell lines were propagated in vitro. Natural curcumin was obtained commercially, while RL66 and RL118 were synthesized and characterized de novo. Multi-well fluorescent/luminescent signal detection was utilized to simultaneously ascertain cell viability, cell cytonecrosis, and relative amounts of apoptotic activity. AHR activity was measured with a dual luciferase reporter gene system. Stable expression of siRNA interference was established in the HCT116 cell lines to create AHR “knock down” cell lines. RESULTS Both RL66 and RL118 proved to be more potent antitumor agents than their parent compound curcumin in all cell lines tested. The majority of this cell death was due to induction of apoptosis, which occurred earlier and to a greater degree following RL66 and RL118 treatment as opposed to curcumin. Also, RL66 and RL118 were found to be activators of AHR, and a portion of their ability to cause cell death was dependent on this induction. Curcumin was found unable to activate the AHR, and levels of AHR mRNA did not change its effects on cell death. CONCLUSION Piperidone analogs of curcumin exhibited enhanced antitumor effects in vitro as opposed to their parent compound. Even more, this enhanced cell death profile may be partially attributed to the ability of these compounds to activate the AHR. Further study of synthetic curcumin analogs as chemopreventives and chemoadjuncts in CRC is warranted. Also, more generally, the AHR may represent a potential putative target for novel anticancer agents for CRC.

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Section: Methodssupporting

confidence: 90%

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

Megna

Carney

Depke

et al. 2017

Journal of Surgical Research

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“…Recently, instead of aryl substituents, the use of heterocyclic ligands was suggested, as these are able to bind important metal cations to form diverse coordination associates (Vatsadze et al, 2006). However, to our knowledge, there are very few structurally characterized compounds of this type in the literature (Vatsadze et al, 2006).…”

Section: Commentmentioning

confidence: 99%

“…However, to our knowledge, there are very few structurally characterized compounds of this type in the literature (Vatsadze et al, 2006). In this paper, we describe two new cross-conjugated piperidones with thienylidene substituents in the side chains, namely 1-methyl-3,5-bis[(E)-2-thienylidene]-4-piperidone, (I), and 3,5-bis[(E)-5-bromo-2-thienylidene]-1-methyl-4-piperidone, (II), which represent modified analogs of the recently reported compounds 2,6-bis[(2-thienyl)methylidene]cyclohexanone, (III) (Vatsadze et al, 2006), and 2,6-bis[(5-methylthiophene-2-yl)methylene]-cyclohexanone, (IV) (Liang et al, 2007) (see scheme above). One purpose of our investigation was to analyze the influence of small structural modifications of the molecules on their structurally dependent properties.…”

Section: Commentmentioning

confidence: 99%

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From small structural modifications to adjustment of structurally dependent properties: 1-methyl-3,5-bis[(E)-2-thienylidene]-4-piperidone and 3,5-bis[(E)-5-bromo-2-thienylidene]-1-methyl-4-piperidone

et al. 2009

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The molecules of the title compounds, C 16 H 15 NOS 2 , (I), and C 16 H 13 Br 2 NOS 2 , (II), are E,E-isomers and consist of an extensive conjugated system, which determines their molecular geometries. Compound (I) crystallizes in the monoclinic space group P2 1 /c. It has one thiophene ring disordered over two positions, with a minor component contribution of 0.100 (3). Compound (II) crystallizes in the noncentrosymmetric orthorhombic space group Pca2 1 with two independent molecules in the unit cell. These molecules are related by a noncrystallographic pseudo-inversion center and possess very similar geometries. The crystal packings of (I) and (II) have a topologically common structural motif, viz. stacks along the b axis, in which the molecules are bound by weak C-HÁ Á ÁO hydrogen bonds. The noncentrosymmetric packing of (II) is governed by attractive intermolecular BrÁ Á ÁBr and BrÁ Á ÁN interactions, which are also responsible for the very high density of (II) (1.861 Mg m À3). CommentCross-conjugated dienones of the bis-arylidenecycloalkanone series and related piperidones have recently attracted considerable attention. These compounds are used in the construction of different polymers (Yakimansky et al., 2002;Aly et al., 2003), and in the design of crystals with nonlinear optical (Kishore & Kishore, 1993;Kawamata et al., 1995Kawamata et al., , 1996Sarkisov et al., 2005) and fluorescent (Nesterov et al., 2003(Nesterov et al., , 2008 properties. Furthermore, it is well known that they possess a variety of biological activities, such as antiviral (ElSubbagh et al., 2000), antibacterial (Lyrand et al., 1999;Amal Raj et al., 2003) and antiphlogistic activity (Rovnyak et al., 1982).Recently, instead of aryl substituents, the use of heterocyclic ligands was suggested, as these are able to bind important metal cations to form diverse coordination associates One purpose of our investigation was to analyze the influence of small structural modifications of the molecules on their structurally dependent properties. It should be noted that these compounds are potential antitumor (anticancer) agents (Dimmock et al., 1992(Dimmock et al., , 1994(Dimmock et al., , 2001, and even small differences in the structures may cause significant changes in their biological activity.Compound (I) crystallizes in the monoclinic space group P2 1 /c. One thiophene ring is disordered over two positions related by a 180 rotation about the C6-C7 bond. The minor component contribution refined to 0.100 (3) (Fig. 1). The molecular structure of (I), showing the atom-numbering scheme. The alternative position of the disordered thiophene ring is drawn with open lines. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.

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Synthesis and Spectroscopic and Structural Studies of Cross‐Conjugated Dienones Derived from Cyclic Ketones and Aromatic Aldehydes.

Abstract: 32 examples) is prepared from readily available ketones (I). -(VATSADZE*, S. Z.; MANAENKOVA, M. A.; SVIRIDENKOVA, N. V.; ZYK, N. V.; KRUT'KO, D. P.; CHURAKOV, A. V.; ANTIPIN, M. Y.; HOWARD, J. A. K.; LANG, H.; Russ.

Cited by 2 publications

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The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

From small structural modifications to adjustment of structurally dependent properties: 1-methyl-3,5-bis[(E)-2-thienylidene]-4-piperidone and 3,5-bis[(E)-5-bromo-2-thienylidene]-1-methyl-4-piperidone

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