Degradation and Inactivation of Antitumor Drugs

Benvenuto, John A.; Connor, Thomas H.; Monteith, David K.; Laidlaw, Jana L.; Adams, Stephen; Matney, Thomas S.; Theiss, Jeffrey C.

doi:10.1002/jps.2600821007

Cited by 76 publications

(86 citation statements)

References 5 publications

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“…The cytotoxicity of the synthesized derivatives was determined using the PI fluorescence method 35,42 in the presence of different concentrations (1-100 lM) of these compounds.…”

Section: Cytotoxicitymentioning

confidence: 99%

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Liargkova

Hadjipavlou‐Litina

Koukoulitsa

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen-Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.

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“…The cytotoxicity of the synthesized derivatives was determined using the PI fluorescence method 35,42 in the presence of different concentrations (1-100 lM) of these compounds.…”

Section: Cytotoxicitymentioning

confidence: 99%

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Liargkova

Hadjipavlou‐Litina

Koukoulitsa

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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show abstract

“…These novel compounds are principally conjugated unsaturated ketones which are known to react with thiols [1] but have low or nonexistent affinities for amino and hydroxy groups [2,3]. Since thiols, in contrast to amino or hydroxy groups, are not found in nucleic acids, α, β-unsaturated ketones may be bereft of the carcinogenic and mutagenic properties displayed by various anticancer drugs [4]. There are a number of critical biochemical processes which involve thiols and the importance of compounds which interact with multiple molecular targets has been emphasized recently [5,6].…”

Section: Introductionmentioning

confidence: 99%

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

Pati

Das

et al. 2009

European Journal of Medicinal Chemistry

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This study demonstrated that replacement of the axial protons on the C2 and C6 atoms of various 1-methyl-3,5-bis(benzylidene)-4-piperidones 3 by a dimethylene bridge leading to series 2 lowered cytotoxic potencies. Four compounds 2a and 3a-c emerged as lead molecules based on their toxicity towards different neoplasms and their selective toxicity for malignant rather than normal cells. Some possible reasons for the disparity between the IC 50 values in the two series of compounds are presented based on molecular modeling, log P values and respiration in rat liver mitochondria.

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“…This decision is based on their preferential affinity towards thiols rather than hydroxy or amino groups [1][2][3]. Hence such molecules may not interact with nucleic acids and thus be bereft of the genotoxic effects of many anticancer drugs used today [4]. Originally only one conjugated arylidene keto group was present in the molecules.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic 3,5-bis(benzylidene)piperidin-4-ones and N-acyl analogs displaying selective toxicity for malignant cells

Pati

Das

Quail

et al. 2008

European Journal of Medicinal Chemistry

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A series of 3,5-bis(benzylidene)piperidin-4-ones 1, 1-acryloyl-3,5-bis(benzylidene)piperidin-4-ones 2 and adducts of 2 with sodium 2-mercaptoethanesulfonate (mesna), namely series 3, were prepared as candidate cytotoxic agents. These compounds were examined against neoplastic HSC-2, HSC-4 and HL-60 cells as well as HGF, HPC and HPLF normal cell lines and many of the compounds displayed selective toxicity for malignant cells. The CC 50 values of the analogs in series 2 towards the cancer cell lines were mainly submicromolar. The relative potencies, selectivity and log P values were in the order of 2 > 1 > 3. The sulfonic acid group of a representative compound in series 3 was replaced by a thiol function to produce 4 leading to substantial increases in cytotoxic potencies and hydrophobicity indicating that the presence of a hydrophilic sulfonic acid group was disadvantageous in terms of potency. Molecular modeling suggested that the superior cytotoxicity of various members of series 1-3 over an acyclic analog 5 may have been due to the greater torsion angles θ 1 and θ 2 created between the arylidene aryl rings and the adjacent olefinic groups in series 1-3.

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Degradation and Inactivation of Antitumor Drugs

Cited by 76 publications

References 5 publications

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

Cytotoxic 3,5-bis(benzylidene)piperidin-4-ones and N-acyl analogs displaying selective toxicity for malignant cells

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