Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones

Lee, Hyunjung; Kim, Jin Sung; Park, Se-Young; Suh, Myung-Eun; Kim, Hwa Jung; Seo, Eun-Kyung; Lee, Chong‐Ock

doi:10.1016/j.bmc.2004.01.029

Cited by 46 publications

(20 citation statements)

References 14 publications

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“…Several derivatives were prepared but no one exhibited better cytotoxicity respect to the parent compounds although the ED 50 values of 0.007-0.061 lg/mL against SK-OV-3 tumour cell line were approximately 3-22-fold lower that that of doxorubicin Fig. 11.9 Chemical structure of phenazine-6,11-dione and analogs (38)(39)(40)(41)(42)(43)(44)(45) (ED 50 = 0.160 lg/mL) (Lee et al 2004). In general pyridophenazinediones possessing three nitrogen atom shown much better cytotoxicity than benzophenazinediones possessing two nitrogen atoms (Kim et al 2003) according to the results of Johnson (Shaikh et al 1986), which reported that the number of nitrogen atoms are important for cytotoxicity.…”

Section: Dimeric Phenazinesmentioning

confidence: 95%

“…6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione (38, Fig. 11.9) exhibited a much greater cytotoxic activity upon the growth of all the human tumour cell lines tested than those of doxorubicin with ED 50 values of 0.007-0.041 lg/mL against human lung (A549), human ovarian (SK-OV-3), human melanoma (SK-MEL-2), human CNC (XF 498) and human colon (HCT 15) cell lines (Lee et al 2004). Several derivatives were prepared but no one exhibited better cytotoxicity respect to the parent compounds although the ED 50 values of 0.007-0.061 lg/mL against SK-OV-3 tumour cell line were approximately 3-22-fold lower that that of doxorubicin Fig.…”

Section: Dimeric Phenazinesmentioning

confidence: 97%

“…6, 11-dihydro-pyridazo[2,3-b]phenazine-6, 11-dione (39, Fig. 11.9) tetracyclic heteroquinone with four nitrogen atoms exhibited potent cytotoxic activity against all the tumour cell lines tested, and in particular its cytotoxic effect against HCT 15 (ED 50 0.004 lg/mL) was 25 times greater than that of doxorubicin (ED 50 0.093 lg/mL) (Lee et al 2004).…”

Section: Dimeric Phenazinesmentioning

confidence: 99%

“…Lee and coworkers, focused on the synthesis and cytotoxic evaluation of nitrogen containing heterocyclic quinones such as 6,11-dihydrobenzo[2,3-b]phenazine-6,11-dione and their analogs (benzophenazinediones) (Kim et al 2003), 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione and their analogs (pyridophenazinediones) (Kim et al 2003;Lee et al 2004) and 6,11-dihydro-pyridazo[2,3-b]phenazine-6,11-dione (also known as 6,11-dihydro-quinoxalino[2,3-b]phtalazine-6,11-dione) and their analogs (pyridazophenazine diones) (Lee et al 2004(Lee et al , 2007. 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione (38, Fig.…”

Section: Dimeric Phenazinesmentioning

confidence: 99%

See 3 more Smart Citations

Phenazine as an Anticancer Agent

Cimmino¹,

Andolfi²,

Evidente³

2013

Microbial Phenazines

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Since 1859, when Fordos reported the isolation of the blue pigment 5-N-methylphenazine-1-one, named pyocyanin, more than 100 different natural phenazines have been isolated and more of 6,000 compounds with a phenazinebased skeleton have been synthesised. The biological activities of these compounds including antimicrobial, antimalarial and antiparasitic activities have been reported, although since 1959, phenazines have been associated with anticancer activity and several publication and patents are available thus far. This chapter critically discusses the structural features of both natural and synthetic phenazines in relation to their in vitro, in vivo and available clinical anticancer activity along with a focus on the mode of action.

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Section: Dimeric Phenazinesmentioning

confidence: 95%

Section: Dimeric Phenazinesmentioning

confidence: 97%

Section: Dimeric Phenazinesmentioning

confidence: 99%

Section: Dimeric Phenazinesmentioning

confidence: 99%

See 2 more Smart Citations

Phenazine as an Anticancer Agent

Cimmino¹,

Andolfi²,

Evidente³

2013

Microbial Phenazines

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show abstract

“…The antitumor activity of nitrogen-containing heterocyclic quinones such as benzophenazinedione 1 [Kim et al, 2003a], pyridophenazinedione 2 [Kim et al, 2003a;Lee et al, 2004], pyridazophenazinedione 3 [Lee et al, 2004, pyridophenazinedione 4 , and azabenzofluorenedione 5 [Kim et al, 2003b;Lee et al, 2007] has been previously reported (Fig. 1).…”

Section: Introductionmentioning

confidence: 96%

3D‐QSAR studies of cytotoxic heterocyclic quinones using calculated reduction potential

Lee¹,

Kim²,

Rhee³

et al. 2009

Drug Development Research

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Most quinones with 2-4 fused aromatic rings exhibit cytostatic activity via DNA intercalation that causes enzyme blockade and reading errors during the replication process. The redox activity of quinones plays a role in the DNA cleavage mediated by oxygen or sulfur radicals. To develop novel anticancer agents based on nitrogen-containing heterocyclic quinones, pharmacophore models of representative molecules with high activity were generated using Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). A series of compounds were aligned to the selected pharmacophore model and the 3D-quantitative structure activity relationships (QSAR) were analyzed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), resulting in q 2 values of 0.734 and r 2 of 0.951, and q 2 of 0.803 and r 2 of 0.917, respectively, in each study. In addition, the potentials for the one-electron reduction of quinones were calculated from LUMO energies using the semi-empirical Austin Model 1 (AM1) method. These also showed a good correlation (r 2 of 0.816) with the cytotoxic activities of the quinones. Drug Dev Res 70 : 438-444, 2009.

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Synthesis of a New Library of Pyrano‐phenazine Derivatives via a Novel Three‐Component Protocol

Shaabani

Ghadari

Arabieh

2014

Helvetica Chimica Acta

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The pyrano‐phenazine derivatives 6 were synthesized by an efficient procedure using the reaction between benzo[a]phenacin‐5‐ols with the condensation product of an aldehyde with Meldrum's acid in the presence of a catalytic amount of Et3N at ambient temperature. The procedure is very simple, and products could be separated from the reaction media by simple filtration. High functional‐group tolerance both in the benzo[a]phenazin‐5‐ol and aldehyde moieties, facile reaction procedure, medium‐to‐high yields, and simple separation of the products from the reaction media are the advantages of this route.

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Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones

Cited by 46 publications

References 14 publications

Phenazine as an Anticancer Agent

Phenazine as an Anticancer Agent

3D‐QSAR studies of cytotoxic heterocyclic quinones using calculated reduction potential

Synthesis of a New Library of Pyrano‐phenazine Derivatives via a Novel Three‐Component Protocol

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