Synthesis and Cytotoxic Activity of Carboxamide Derivatives of Benzo[<i>b</i>][1,6]naphthyridines

Deady, Leslie W.; Rodemann, Thomas; Li, Zhuang; Baguley, Bruce C.; Denny, William A.

doi:10.1021/jm020420u

Cited by 65 publications

(47 citation statements)

References 20 publications

(56 reference statements)

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“…The results suggest a novel action for SN 28049 and DACA; namely that drug-induced suppression of topo I activity acts as a chemosensitiser for topo II-targeted cytotoxicity. This could help explain the in vivo high activity of SN 28049 and DACA against the Colon 38 murine adenocarcinoma in vivo [20,30].…”

Section: Discussionmentioning

confidence: 92%

“…1). Several compounds in this series were able to induce complete regression of subcutaneous implants of the Colon 38 adenocarcinoma, a tumour which is relatively resistant to topo II-directed drugs such as amsacrine, doxorubicin and etoposide [20]. SN 28049 is approximately 50-fold more potent than DACA in vitro and 20-fold more dosepotent in vivo.…”

Section: Introductionmentioning

confidence: 99%

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The role of topoisomerases and RNA transcription in the action of the antitumour benzonaphthyridine derivative SN 28049

Bridewell¹,

Porter²,

Finlay³

et al. 2008

Cancer Chemother Pharmacol

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Purpose-SN 28049 (N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide) is a DNA intercalating drug that binds selectively to GC-rich DNA and shows curative activity against the Colon 38 adenocarcinoma in mice. We wished to investigate the roles of topoisomerase (topo) I, topo II and RNA transcription in the action of SN 28049.Methods-We used clonogenic assays to study the cytotoxicity of SN 28049; RNA interference and enzyme assays to examine the role of topo I in SN 28049 action; 3 H uridine incorporation and reporter assays to study its effects on transcription; and RT-PCR to examine its ability to reduce endogenous h-TERT expression. Conclusion-We conclude that SN 28049 has a complex action that may involve poisoning of topo IIα, suppression of topo I and inhibition of gene transcription from promoters with SP-1 sites. These actions may contribute to the promising experimental solid tumour anticancer activity of SN 28049. Results-In

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

The role of topoisomerases and RNA transcription in the action of the antitumour benzonaphthyridine derivative SN 28049

Bridewell¹,

Porter²,

Finlay³

et al. 2008

Cancer Chemother Pharmacol

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“…This has several biological implications, 11,12 including anti-HSV property. 13 Furthermore, the organic molecules with fluorescent properties have added advantages to its biological applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of multi ring-fused imidazo [1,2-a]isoquinoline-based fluorescent scaffold as anti-Herpetic agent

Chakravarty

Ojha

Konreddy

et al. 2015

Antivir Chem Chemother

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Background: Natural product-inspired synthesis is a key incorporation in modern diversity-oriented synthesis to yield biologically novel scaffold. Inspired by b-carboline fused system, we have designed molecules with multi ring fused scaffold by modifying the tricyclic pyrido [3,4-b]indole ring with imidazo[1,2-a]isoquinoline. Methods: A highly convergent approach with new C-N and C-C bond formation to synthesize multiring fused complex scaffold imidazo[1,2-a]isoquinolinies as fluorophores. N-nucleophile-induced ring transformation of 2H-pyran-2-one followed by in situ cis-stilbene-type oxidative photocyclization yielded new C-C bond formation without additional oxidant. The cytotoxicity, effective concentrations, and the mode of action of the synthesized analogs were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),, plaque reduction, time of addition, and reverse transcriptase Polymerase Chain Reaction (PCR). Results: Novel imidazo[1,2-a]isoquinoline analogs were prepared, and the results revealed that trans isomer of cyclopropyl analog (EC 50 35 and 37.5 mg/ml) and trans isomer of citric acid salt of phenyl analog (EC 50 38.2 and 39.8 mg/ml) possess significant anti-Herpes Simplex Virus (HSV) activity with selectivity index of >10. The kinetic study demonstrated that both the analogs inhibited HSV-1F and HSV-2G at 2-4 h postinfection. Finally, western blot and reverse transcriptase PCR assays revealed that both the analogs suppressed viral immediate early transcription. Conclusion: Novel imidazo[1,2-a]isoquinoline analogs were synthesized from pyranone with appropriate amines. Two compounds showed better antiviral profile on HSV-infected Vero cells, compared to the standard drug acyclovir (ACV). Overall, we discovered a promising scaffold to develop a nonnucleoside lead targeting the viral immediate early transcription for the management of HSV infections.

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“…[1][2][3] Benzimidazole-based ployhetrocycles has exhibited interesting biological properties. For example, benzimidazoquinazolines, 4-8 benzimidazoisoquinolines 9 and benzimidazo[2,1-a]isoindolones 10 were reported as potent antitumor agents. Benzimidazo [2,1-b]quinazolines are potent immuno-suppressors 11 and benzimidazo [2,1-b] are also known to be sedatives and tranquilizers.…”

Section: Introductionmentioning

confidence: 99%

Synthetic routes to benzimidazole-based fused polyheterocycles

Dawood¹,

Abdel‐Wahab²

2010

Arkivoc

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The review article represents a survey covering the synthetic strategies leading to benzimidazolebased fused polyheterocyclic systems utilizing simple reactive benzimidazole synthons since 1980. The polyheterocyclic systems are classified based on the number of rings; tetra-, penta-, hexa-and hepta-fused ring systems. Among each polyheterocyclic system, further classification according to the number of heterotoms; two-, three-, four-, five-, six-and seven heteroatoms is considered.

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Synthesis and Cytotoxic Activity of Carboxamide Derivatives of Benzo[b][1,6]naphthyridines

Cited by 65 publications

References 20 publications

The role of topoisomerases and RNA transcription in the action of the antitumour benzonaphthyridine derivative SN 28049

The role of topoisomerases and RNA transcription in the action of the antitumour benzonaphthyridine derivative SN 28049

Synthesis of multi ring-fused imidazo [1,2-a]isoquinoline-based fluorescent scaffold as anti-Herpetic agent

Synthetic routes to benzimidazole-based fused polyheterocycles

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