Selective thromboxane synthetase inhibitors. 3. 1H-Imidazol-1-yl-substituted benzo[b]furan-, benzo[b]thiophene- and indole-2- and 3-carboxylic acids

Pe, Cross; Rp, Dickinson; Mj, Parry; Mj, Randall

doi:10.1021/jm00159a012

Cited by 14 publications

(2 citation statements)

References 2 publications

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“…Accordingly, hybrid compounds with active moieties of known antitumor and antiviral agents are being designed and synthesized to provide highly sequence-selective DNA-interactive properties and antitumor activities . Because DC-81 and indole carboxylate moieties are commonly used as medicinal compounds, for example, as antimitotic drugs – , we synthesized a hybrid (IN6CPBD, Figure ) from DC-81 coupled with an indole carboxylate moiety . We expected that IN6CPBD would recognize more DNA base pairs and bind sequence selectively to the macromolecule.…”

Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis by DC-81-Indole Conjugate Agent Through NF-κB and JNK/AP-1 Pathway

Tsai

et al. 2008

Chem. Res. Toxicol.

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DC-81, an antitumor antibiotic produced by Streptomyces species, belongs to the pyrrolo[2,1- c][1,4]benzodiazepine (PBD) family, which are potent inhibitors of nucleic acid synthesis. We previously reported an efficient synthesis of PBD hybrids linked with indole carboxylates. Recently, we have also shown that a PBD hybrid (IN6CPBD) agent can activate the apoptotic pathway mediated by mitochondria. In this study, we will examine the transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) that functionally regulate cell proliferation, transformation, and apoptosis. To investigate the IN6CPBD-induced alterations in NF-kappaB and AP-1 activity that involve cell cycle regulation, we exposed human melanoma A375 cells to different concentrations of IN6CPBD. Our data revealed that treatment of A375 cells with IN6CPBD resulted in a marked loss of cells from the G2/M phase of the cell cycle and an increase in Ca (2+) and cAMP and promoted phosphorylation of Jun N-terminal kinase (JNK) expression. By using the luciferase reporter assay, the NF-kappaB activities were decreased; however, AP-1 activity was further enhanced after A375 cells were treated with graded concentrations of IN6CPBD. Blockade of NF-kappaB or JNK activity further enhanced caspase-3 substrate PARP cleavage and subsequent apoptotic cell death.

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Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis by DC-81-Indole Conjugate Agent Through NF-κB and JNK/AP-1 Pathway

Tsai

et al. 2008

Chem. Res. Toxicol.

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“…DC-81 and indole carboxylate are commonly used as medicinal compounds, e.g. as antimitotic drugs [17][18][19]. We expected that hybrid 3 would recognize more DNA base pairs and bind sequenceselectively to the macromolecule.…”

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confidence: 99%

Biological Evaluation of an Antibiotic DC‐81–Indole Conjugate Agent in Human Melanoma Cell Lines

Chen

Wang

et al. 2003

The Kaohsiung J of Med Scie

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Pyrrolo[2, 1-c][1, 4]benzodiazepines (PBDs) are potent inhibitors of nucleic acid synthesis because of their ability to recognize and bind to specific sequences of DNA and form a labile covalent adduct. DC-81, an antitumor antibiotic produced by Streptomyces species, is a PBD. We combined DC-81 and an indole carboxylate moiety to synthesize a hybrid designed to have much higher sequence selectivity in DNA interactivity. In this paper, the cytotoxic potency of the hybrid in human melanoma cell lines was studied. XTT assay demonstrated that the DC-81-indole conjugate possessed cytotoxicity against human melanoma cell lines.

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ChemInform Abstract: Selective Thromboxane Synthetase Inhibitors. Part 3. 1H‐Imidazol‐1‐yl‐ Substituted Benzo(b)furan‐, Benzo(b)thiophene‐, and Indole‐2‐ and ‐3‐carboxylic Acids.

Cross¹,

Dickinson²,

Parry³

et al. 1987

ChemInform

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Selective thromboxane synthetase inhibitors. 3. 1H-Imidazol-1-yl-substituted benzo[b]furan-, benzo[b]thiophene- and indole-2- and 3-carboxylic acids

Cited by 14 publications

References 2 publications

Induction of Apoptosis by DC-81-Indole Conjugate Agent Through NF-κB and JNK/AP-1 Pathway

Induction of Apoptosis by DC-81-Indole Conjugate Agent Through NF-κB and JNK/AP-1 Pathway

Biological Evaluation of an Antibiotic DC‐81–Indole Conjugate Agent in Human Melanoma Cell Lines

ChemInform Abstract: Selective Thromboxane Synthetase Inhibitors. Part 3. 1H‐Imidazol‐1‐yl‐ Substituted Benzo(b)furan‐, Benzo(b)thiophene‐, and Indole‐2‐ and ‐3‐carboxylic Acids.

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