Anticancer anthrapyrazoles. The synthesis of 2‐substituted 5‐nitro and 5‐aminoanthra[1,9‐<i>cd</i>]pyrazol‐6(2<i>H</i>)‐ones

Showalter, H. D. Hollis; Turner, William R.

doi:10.1002/jhet.5570300236

Cited by 5 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,11-Dihydroxy-6-[(aminoalkyl)amino]-substituted benzoperimidines 6a − g were synthesized by two methods using 1,4-diamino-5,8-bis(phenylmethoxy)-9,10-anthracenedione ( 3 ) (method A) or 1-hydroxy-4-nitro-5,8-bis(phenylmethoxy)-9,10-anthracenedione ( 7 ) (method B) as starting materials (see Scheme ). 6-Amino-8,11-bis(phenylmethoxy)-7 H -benzo[ e ]perimidin-7-one ( 4 ) was obtained by refluxing 1,4-diamino-5,8-bis(phenylmethoxy)-9,10-anthracenedione ( 3 ) with formamide in the presence of ammonium metavanadate in dimethylacetamide (method A).…”

Section: Chemistrymentioning

confidence: 99%

8,11-Dihydroxy-6-[(aminoalkyl)amino]-7H-benzo[e]perimidin-7-ones with Activity in Multidrug-Resistant Cell Lines: Synthesis and Antitumor Evaluation

Stefańska

Dzieduszycka

et al. 1999

J. Med. Chem.

View full text Add to dashboard Cite

The synthesis of dihydroxybenzoperimidine derivatives, which are chromophore-modified dihydroxyanthracenediones with an additional pyrimidine ring incorporated into the chromophore, is reported. These derivatives are structurally related to the antitumor agent mitoxantrone. Their synthesis was carried out by the reaction of 6-amino-8,11-dihydroxy-7H-benzo[e]perimidin-7-one (5) or 6,8,11-trihydroxy-7H-benzo[e]perimidin-7-one (10) with a number of respective (alkylamino)alkylamines. The dihydroxybenzoperimidine derivatives exhibited in vitro cytotoxic activity against murine leukemia L1210 and human leukemia HL60 cell lines comparable to that of mitoxantrone. These compounds also exhibited a range of in vitro activity against the human MDR-type resistant leukemia K562R cell line with the MDR phenotype. The most active compound of this series, namely 6a, exhibited potent in vitro cytotoxic activity against a panel of human cell lines. Furthermore, in contrast to both mitoxantrone and doxorubicin, it displayed little cross-resistance in cell lines characterized by a MDR phenotype. Cell cycle analysis in the sensitive HT-29 and mitoxantrone-resistant HT-29/Mx (not identified resistance mechanism) cell lines has revealed that both mitoxantrone and 6a induce a G2/M block. However, while the proportion of apoptotic cells after mitoxantrone treatment is similar for both sensitive and resistant cell lines, it is much lower for 6a. Compound 6a tested against P388 murine leukemia in vivo displayed a significant antitumor effect (%T/C 196 at an optimal dose of 10 mg/kg). The property of overcoming the cross-resistance was maintained also in in vivo efficacy studies, where no difference was observed in the antitumor activity of compound 6a against the A2780 human tumor xenograft and its MDR A2780/Dx subline. We conclude that benzoperimidines, if properly substituted, constitute a novel class of compounds that can overcome multidrug resistance.

show abstract

Section: Chemistrymentioning

confidence: 99%

8,11-Dihydroxy-6-[(aminoalkyl)amino]-7H-benzo[e]perimidin-7-ones with Activity in Multidrug-Resistant Cell Lines: Synthesis and Antitumor Evaluation

Stefańska

Dzieduszycka

et al. 1999

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] DNA intercalating agents interfere with DNA's role as a template in replication and transcription by inserting an intercalator molecule between adjacent base pairs. 5) Of the drug-receptor interactions studied in recent years, the intercalation of planar aromatic molecules between consecutive base pairs of a DNA double helix is one of the most appealing at the molecular level.…”

mentioning

confidence: 99%

Studies on Anthracenes. 2. Synthesis and Cytotoxic Evaluation of 9-Acyloxy 1,8-Dichloroanthracene Derivatives.

Huang

Chiu

Hwang

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The synthesis and cytotoxic evaluation of 9-acyloxy 1,8-dichloroanthracene derivatives are described. The system selectively reduces the carbonyl group flanked by the peri substituents of the anthracenediones to give the corresponding 1,8-dichloro-9(10H)-anthracenone. Simple acylation of anthracenone occurred with appropriate acyl chlorides in CH 2 Cl 2 with a catalytic amount of pyridine to give the 9-acyloxy-1,8-dichloroanthracene derivatives. Considerable interest has developed in the mechanism of how anthracenones achieve this desirable selectivity. These compounds were evaluated in vitro for their ability to inhibit the growth of human oral epidermoid carcinoma cells (KB cell line), human cervical carcinoma cells of ME 180 (GBM 8401) and Chinese hamster ovary (CHO) cells, respectively, as compared to mitoxantrone. The in vitro cytotoxicity evaluation of 9-acyloxy 1,8-dichloroanthracenes against these above cell lines revealed for most of the compounds a cytotoxic potency lower than that of mitoxantrone. The most active compounds were thus selected for further in vitro biological evaluation and structural modification.

show abstract

ChemInform Abstract: Anticancer Anthrapyrazoles. The Synthesis of 2‐Substituted 5‐Nitro and 5‐Aminoanthra(1,9‐cd)pyrazol‐6(2H)‐ones.

Showalter¹,

Turner²

1993

ChemInform

View full text Add to dashboard Cite

show abstract

Anticancer anthrapyrazoles. The synthesis of 2‐substituted 5‐nitro and 5‐aminoanthra[1,9‐cd]pyrazol‐6(2H)‐ones

Cited by 5 publications

References 14 publications

8,11-Dihydroxy-6-[(aminoalkyl)amino]-7H-benzo[e]perimidin-7-ones with Activity in Multidrug-Resistant Cell Lines: Synthesis and Antitumor Evaluation

8,11-Dihydroxy-6-[(aminoalkyl)amino]-7H-benzo[e]perimidin-7-ones with Activity in Multidrug-Resistant Cell Lines: Synthesis and Antitumor Evaluation

Studies on Anthracenes. 2. Synthesis and Cytotoxic Evaluation of 9-Acyloxy 1,8-Dichloroanthracene Derivatives.

ChemInform Abstract: Anticancer Anthrapyrazoles. The Synthesis of 2‐Substituted 5‐Nitro and 5‐Aminoanthra(1,9‐cd)pyrazol‐6(2H)‐ones.

Contact Info

Product

Resources

About