Evaluation of some Mannich bases of cycloalkanones and related compounds for cytotoxic activity

Dimmock, J. R.; Sidhu, K. K.; Chen, M; Reid, R. S.; Allen, T. W.; Kao, G. Y.; Ga, Truitt

doi:10.1016/0223-5234(93)90148-8

Cited by 55 publications

(33 citation statements)

References 19 publications

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“…However with the aim of preparing conjugated enones with selective or preferential toxicity to malignant cells rather than the corresponding normal cells, the theory of sequential cytotoxicity was proposed [8]. This hypothesis states that a chemical insult prior to a subsequent chemical attack on cellular constituents may produce greater toxicity to cancers than normal cells.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…3 Recently molecules have been designed to enable successive alkylation of thiols to occur since on occasion sequential reactions with cellular constituents have been claimed to be more detrimental to malignant cells than the corresponding normal tissues. 4 These considerations led to the decision to prepare a number of compounds which contain the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore (ArCH=CR-CO-CR=CHAr) 5,6 thereby allowing stepwise alkylation of cellular thiols. Recently a small number of 2,6-bis(benzylidene) cyclohexanones were prepared in which the substituents in each of the aryl rings differed in their electronic properties.…”

Section: Introductionmentioning

confidence: 99%

E,E-2-Benzylidene-6-(nitrobenzylidene)cyclohexanones: Syntheses, cytotoxicity and an examination of some of their electronic, steric, and hydrophobic properties

Das

Doroudi

Das

et al. 2008

Bioorganic & Medicinal Chemistry

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Three series of structurally isomeric 2-benzylidene-6-(nitrobenzylidene) cyclohexanones 1-3 were prepared and evaluated against human Molt/C8 and CEM T-lymphocytes as well as murine L1210 cells. The IC 50 values of the majority of compounds are less than 10 μM and in some assays, the figures for 1d and 1e are submicromolar. Correlations were discerned between cytotoxic potencies and the atomic charges on one of the olefinic carbon atoms, the torsion angles between an aryl ring, and the adjacent unsaturated group as well as logP values. Three representative compounds were examined for their effect on respiration in rat liver mitochondria.

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“…A number of Mannich ketones (MKs)-as a special type of this family-could show more selective toxicity toward microorganisms than the parent unsaturated ketones [18]. Beyond their antimicrobial effect, several MKs are described to have cytotoxic activity [19][20][21][22]. All these compounds are potential alkylating reagents.…”

Section: Introductionmentioning

confidence: 98%

Determination of the basicity of Mannich ketones by capillary electrophoresis

Dobos¹,

Lóránd²,

Hollósy³

et al. 2004

Journal of Chromatography B

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Evaluation of some Mannich bases of cycloalkanones and related compounds for cytotoxic activity

Cited by 55 publications

References 19 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

E,E-2-Benzylidene-6-(nitrobenzylidene)cyclohexanones: Syntheses, cytotoxicity and an examination of some of their electronic, steric, and hydrophobic properties

Determination of the basicity of Mannich ketones by capillary electrophoresis

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