Synthesis and cytotoxicity of 6,11-Dihydro-pyrido- and 6,11-Dihydro-benzo[2,3-b]phenazine-6,11-dione derivatives

Kim, Young-Shin; Park, Se-Young; Lee, Hyunjung; Suh, Myung-Eun; Schollmeyer, Dieter; Lee, Chong‐Ock

doi:10.1016/s0968-0896(03)00028-2

Cited by 53 publications

(30 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 5,8-quinolinedione derivatives were among the first compounds to be systematically modified in order to find products with higher biological activities, such as anticancer, anti-inflammatory or antibacterial [1][2][3][4][5][6][7][8][9]. For example, it was found that substitution of the electron-withdrawing groups at the 6-or 7-positions of the 5,8-quinolinedione led to an increase in the DNA degradation [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

New Acetylenic Amine Derivatives of 5,8-Quinolinediones: Synthesis, Crystal Structure and Antiproliferative Activity

et al. 2017

View full text Add to dashboard Cite

Acetylenic amine derivatives of the 5,8-quinolinedione were synthesized and characterized by the 1 H and 13 C NMR, IR spectroscopy and MS spectra. Additionally, the 6-and 7-substituted allylamine-5,8-quinolinediones were synthesized for comparison purposes. The crystal structure was determined for the 6-chloro-7-propargylamine-5,8-quinolinedione and 7-chloro-6-propargylamine-5,8-quinolinedione. Additionally, the IR spectral analysis supplemented by the density functional theory (DFT) calculations were carried out. It was found that different positions of the propargylamine side chain had a distinct influence on crystal structure, formation of H-bonds and the carbonyl stretching IR bands. Correlation between the frequency separation ∆ν of the carbonyl IR bands and the position of the 6-and 7-substituents was found. The 7-substituted derivatives exhibited a higher frequency separation ∆ν. The observed correlation could provide an opportunity to use the IR spectroscopy to study substitution reactions. Cytotoxic activities against three human cancer cell lines for the 5,8-quinolinedione derivatives with different amine substituents, i.e., propargylamine, N-methylpropargylamine, 1,1-dimethylpropargylamine, allylamine and propylamine were also analysed with respect to their molecular structure.

show abstract

Section: Introductionmentioning

confidence: 99%

New Acetylenic Amine Derivatives of 5,8-Quinolinediones: Synthesis, Crystal Structure and Antiproliferative Activity

et al. 2017

View full text Add to dashboard Cite

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: 88%

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

Lee¹,

Kim²,

Rhee³

et al. 2009

Drug Development Research

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Khalifa and coworkers (2008), reported the selective cytotoxicity of 6,11-dihydrobenzo[b]phenazine-6,11-dione (45, Fig. 11.9) against human lung carcinoma cell line (H460), with IC 50 values of 16.25 lM, 1.3 times higher than that of doxorubicin, in contrast with the cytotoxic activity reported by Lee and coworkers for some benzophenazinedione derivatives (Kim et al 2003), in which the IC 50 values against A 549, SK-OV-3, SK-MEL-2, XF 498 and HCT 15 were much higher than that of doxorubicin (Kim et al 2003).…”

Section: Dimeric Phenazinesmentioning

confidence: 95%

“…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%

“…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. 6, 11-dihydro-pyridazo[2,3-b]phenazine-6, 11-dione (39, Fig.…”

Section: Dimeric Phenazinesmentioning

confidence: 99%

See 1 more Smart Citation

Phenazine as an Anticancer Agent

Cimmino¹,

Andolfi²,

Evidente³

2013

Microbial Phenazines

View full text Add to dashboard Cite

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.

show abstract

Synthesis and cytotoxicity of 6,11-Dihydro-pyrido- and 6,11-Dihydro-benzo[2,3-b]phenazine-6,11-dione derivatives

Cited by 53 publications

References 13 publications

New Acetylenic Amine Derivatives of 5,8-Quinolinediones: Synthesis, Crystal Structure and Antiproliferative Activity

New Acetylenic Amine Derivatives of 5,8-Quinolinediones: Synthesis, Crystal Structure and Antiproliferative Activity

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

Phenazine as an Anticancer Agent

Contact Info

Product

Resources

About