Syntheses and Cytotoxic Properties of the Curcumin Analogs 2,6‐Bis(benzylidene)‐4‐phenylcyclohexanones

Davis, Ryan R.; Das, Umashankar; Mackay, Hilary; Brown, Toni; Mooberry, Susan L.; Dimmock, Jonathan R.; Lee, Moses; Pati, Hari N.

doi:10.1002/ardp.200800028

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…Various 2,6-bis(benzylidene)-4-phenylcyclohexanones have IC 50 values in the low micromolar range when evaluated against murine B16 melanoma and L1210 leukemia cell lines and in the case of 39 and 40, the IC 50 figures in the B16 and L1210 assays are 0.51 and 0.35 μM, respectively, and are clearly lead molecules [65]. There is a structural similarity of some of these compounds, particularly those possessing several methoxy aryl substituents, to agents which inhibit tubulin polymerization.…”

Section: Bis(benzylidene)cycloalkanonesmentioning

confidence: 99%

1,5-Diaryl-3-oxo-1,4-pentadienes: A Case for Antineoplastics with Multiple Targets

Das

Sharma²,

Dimmock³

2009

CMC

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A number of organic molecules which contain the 1,5-diaryl-3-oxo-1,4-pentadienyl group, referred to hereafter as the dienone moiety, have antineoplastic properties. Emphasis is made on the attachment of this structural moiety to several molecular scaffolds, namely piperidines, Nacylpiperidines, cycloalkanes and 3,4-dihydro-1H-napthalenes. Many of these compounds are potent cytotoxins having micromolar and nanomolar IC 50 values towards a wide range of neoplastic and transformed cells. On occasions, greater toxicity towards neoplasms than normal cells has been demonstrated. A number of these compounds have in vivo anticancer properties and in general excellent tolerability in rodents is demonstrated. The way in which a number of physicochemical properties such as redox potentials, torsion angles, atomic charges and logP values govern cytotoxic potencies are presented. The importance of the shapes of different compounds as determined by molecular modeling in contributing to antineoplastic properties is outlined. Arguments are presented in favour of designing antineoplastics which have multiple sites of action in contrast to those bioactive molecules which have only one molecular target. A number of compounds which possess the dienone group have different modes of action some of which are chronicled in this review, such as inducing apoptosis, affecting respiration in mitochondria, inhibiting macro-molecular biosynthesis and both inhibiting and stimulating certain enzymes. Other important properties of these compounds are discussed including their anti-angiogenic, MDR-revertant and antioxidant properties. It is hoped that this eulogy of the importance of the dienone group will encourage researchers to consider incorporating this structural unit into candidate cytotoxins in the future.

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Section: Bis(benzylidene)cycloalkanonesmentioning

confidence: 99%

1,5-Diaryl-3-oxo-1,4-pentadienes: A Case for Antineoplastics with Multiple Targets

Das

Sharma²,

Dimmock³

2009

CMC

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“…This indicates that the novel compounds described herein do not act via a similar mechanism of inhibiting cell growth as CA‐4. This is interesting because related bis‐arylidene analogs of the target compounds, which gave equal cytotoxicity, also did not display microtubule disruption properties (34).…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Cytotoxicity of Novel 3‐Arylidenones Derived from Alicyclic Ketones

et al. 2011

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Forty-four novel chalcone-inspired analogs having a 3-aryl-2-propenoyl moiety derived from alicyclic ketones were designed, synthesized, and investigated for cytotoxicity against murine B16 and L1210 cancer cell lines. The analogs belong to four structurally divergent series, three of which (series g, h, and i) contain differently substituted cyclopentanone units and the fourth (series j) contains a 3,3-dimethyl-4-piperidinone moiety. Of these, the analogs in series j showed potential cytotoxic activity against murine B16 (melanoma) and L1210 (lymphoma) cells. The most active compounds 5j, 11j, 15j, and 12h produced IC(50) values from 4.4 to 15 μm against both cell lines. A single-crystal X-ray structure analysis and molecular modeling studies confirmed that these chalcones have an E-geometry about the alkene bond and possess a slightly 'twisted' conformation similar to that of combretastatin A-4. At a concentration of 30 μm, compounds 5j, 11j, and 15j did not cause microtubule depolymerization in cells, suggesting that they have a different mechanism of action.

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“…Structure-activity correlations suggested that large electron-withdrawing substituents placed at the meta-position of the arylidene aryl rings enhance antitumor potencies. The most potent compounds had virtually no effects on microtubules at concentrations up to 40 μM suggesting that tubulin inhibition is not the principal mechanism for their activities [59]. Chen and co workers have studied the antioxidant properties of several Curcumin analogs of 1,6-heptadiene-3,5-dione class 17 (Scheme 1 ) against free radical initiated peroxidation of human low density lipoprotein (LDL) [60].…”

Section: Structural Analogs Of Curcuminmentioning

confidence: 99%

Perspectives on Chemopreventive and Therapeutic Potential of Curcumin Analogs in Medicinal Chemistry

Padhyé¹,

Chavan²,

Pandey³

et al. 2010

MRMC

115

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Curcumin is a natural polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over past 50 years has indicated that this polyphenol is highly pleiotropic molecule capable of preventing and treating various cancers. The anticancer potential of Curcumin is severely affected by its limited systemic and target tissue bioavailability and rapid metabolism. In the present review article, we provide a summarized account of different drug delivery systems employed for tackling the problem of curcumin's bioavailability such as liposomes, phospholipid complexes and nanoparticles. Concomitantly we have reviewed the large volume of literature reports describing structural modifications of Curcumin and the anticancer potential of its analogs. Some of the difluorocurcumin analogs allowing longer circulation times and preferential accumulation in the pancreas seem to offer promising leads for conducting first in-depth animal studies and subsequently clinical trials for the use of these analogs for prevention of tumor progression and/or treatments of human malignancies.

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Syntheses and Cytotoxic Properties of the Curcumin Analogs 2,6‐Bis(benzylidene)‐4‐phenylcyclohexanones

Cited by 12 publications

References 28 publications

1,5-Diaryl-3-oxo-1,4-pentadienes: A Case for Antineoplastics with Multiple Targets

1,5-Diaryl-3-oxo-1,4-pentadienes: A Case for Antineoplastics with Multiple Targets

Design, Synthesis, and Cytotoxicity of Novel 3‐Arylidenones Derived from Alicyclic Ketones

Perspectives on Chemopreventive and Therapeutic Potential of Curcumin Analogs in Medicinal Chemistry

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