Mimicking the biological activity of diazobenzo[b]fluorene natural products with electronically tuned diazofluorene analogs

Zeng, Wei; Ballard, T. Eric; Ткаченко, А. Г.; Burns, Virginia; Feldheim, Daniel L.; Melander, Christian

doi:10.1016/j.bmcl.2006.07.024

Cited by 42 publications

(16 citation statements)

References 18 publications

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“…However, in the lomaiviticin A report [6] the conditions were not given. In the kinamycin D report [10] the incubation that yielded 27% nicked DNA was carried out for a long time (2 d) and at high kinamycin D (1 mM) and DTT concentrations (1 M). These conditions are very different from those used to generate the results shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It was previously reported that lomaiviticin A [6] and kinamycin D [10] could cleave DNA under reducing conditions. However, in the lomaiviticin A report [6] the conditions were not given.…”

Section: Discussionmentioning

confidence: 99%

“…A role for reductive activation of kinamycin D by DTT in its DNA-cleaving ability has also recently been suggested [10]. In the presence of a cupric acetate oxidant the kinamycin F analog 9-diazofluorene was able to nick DNA [11] which suggests possible oxidative activation.…”

Section: Introductionmentioning

confidence: 96%

“…Because two other studies [6,10] indicated that the diazoparaquinones lomaiviticin A and kinamycin D may be able to cleave DNA under reducing conditions, it was decided to investigate whether kinamycin F could cleave DNA under much more physiological conditions. As shown in Fig.…”

Section: Gsh Promotes Kinamycin F-induced Nicking Of Pbr322 Dnamentioning

confidence: 99%

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Mechanism of the cytotoxicity of the diazoparaquinone antitumor antibiotic kinamycin F

O’Hara

Patel

et al. 2007

Free Radical Biology and Medicine

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The bacterial metabolite kinamycin F, which is being investigated as a potent antitumor agent, contains an unusual and potentially reactive diazo group as well as a paraquinone and a phenol functional group. Kinamycin F reacted with glutathione (GSH) in a complex series of reactions which suggested that kinamycin F may have its cytotoxicity modulated by GSH. Consistent with this idea 2-oxo-4-thiazolidinecarboxylic acid treatment to increase cellular GSH levels and buthionine sulfoximine treatment to decrease GSH levels resulted in decreased and increased kinamycin F cytotoxicity, respectively, in K562 leukemia cells. Kinamycin F weakly bound to DNA and induced DNA damage in K562 cells that was independent of GSH levels. The GSH-promoted DNA nicking induced by kinamycin F in vitro was attenuated by deferoxamine, dimethyl sulfoxide, and by catalase, which indicated that DNA damage initiated by this agent occurred in an iron-, hydrogen peroxideand hydroxyl radical-dependent manner. Electron paramagnetic resonance spectroscopy experiments showed that the GSH/kinamycin F system produced a semiquinone free radical and that the hydrogen peroxide/peroxidase/kinamycin F system generated a phenoxyl free radical. In conclusion, the results indicated that kinamycin F cytotoxicity may be due to reductive and/or peroxidative activation to produce DNA-and protein-damaging species.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Gsh Promotes Kinamycin F-induced Nicking Of Pbr322 Dnamentioning

confidence: 99%

See 2 more Smart Citations

Mechanism of the cytotoxicity of the diazoparaquinone antitumor antibiotic kinamycin F

O’Hara

Patel

et al. 2007

Free Radical Biology and Medicine

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“…Diazofluorene 8 : The sample was synthesized from 9‐fluorenone, according to a literature procedure . 1 H NMR (200 MHz, [D 6 ]DMSO): δ =8.08 (d, J =7.8 Hz, 2 H), 7.71 (d, J =7.6 Hz, 2 H), 7.45–7.29 (m, 4 H) ppm; IR (argon, 3 K):

\overset{ν}{true}

=2061 (vs), 1608 (m), 1448 (s), 1443 (s), 1378 (m), 1331 (m), 1310 (m), 1225 (m), 1220 (m), 1155 (m), 752 (s), 725 (s), 653 (m) cm −1 .…”

Section: Methodsmentioning

confidence: 99%

Reactions of Arylcarbenes with Lewis Acids

Raut

Costa

Sander

2018

Chemistry A European J

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The reactions of the three triplet ground state arylcarbenes diphenylcarbene 1, fluorenylidene 2, and dibenzocycloheptadienylidene 3 with the Lewis acids H O, ICF , and BF were studied under the conditions of matrix isolation. H O was selected as typical hydrogen bond donor, ICF as halogen bond donor, and BF as strong Lewis acid. H O forms hydrogen-bonded complexes of the singlet carbenes with 1 and 2, but not with 3. This is rationalized by the larger singlet-triplet gap of 3, which does not allow to stabilize the singlet state below the triplet state by hydrogen bonding. With ICF , both 1 and 3 form halogen-bonded complexes of the singlet states of the carbenes. This indicates that halogen bonding stabilizes singlet carbenes more than hydrogen bonding. Carbene 2 reacts differently from 1 and 3 by forming an iodonium ylide, thus avoiding antiaromatic destabilization of the fluorenyl unit. With BF , all three carbenes form zwitterionic Lewis acid/base complexes.

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Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence

2009

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A stepwise process involving Sonogashira coupling, propargyl-allenyl isomerization and Schmittel cyclization has been realized, leading to an efficient synthesis of polycyclic fluorene derivatives from readily available starting materials. The reaction features the formation of three new carbon-carbon bonds to construct the benzene unit together with an efficient assembly of three or four rings in a single operative step.

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Mimicking the biological activity of diazobenzo[b]fluorene natural products with electronically tuned diazofluorene analogs

Cited by 42 publications

References 18 publications

Mechanism of the cytotoxicity of the diazoparaquinone antitumor antibiotic kinamycin F

Mechanism of the cytotoxicity of the diazoparaquinone antitumor antibiotic kinamycin F

Reactions of Arylcarbenes with Lewis Acids

Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence

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