• Proceedings of the PSK Conference
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• 2003.10b
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• pp.174.1-174.1
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• 2003

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives using doxorubicin as a lead compound. Doxorubicin is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of quinone compounds like Dox, its use is limited because of systemic toxicities, primarily cardiotoxicity and myelosuppression. In this study, we discuss the synthesis of isoindolobenzoquinoxaline derivatives. The quinone group of the azaanthraquinone derivatives were removed in the target compounds. (omitted)

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.380-383
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• 1999

Five 1-azzanthraquinone-3-carboxamides were synthesized and evaluated in vitro cytotoxicity against four human cancer cell lines. The most active compound, 7b, exhibited cytotoxic activity comparable to doxorubicin.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.749-752
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• 1998

Six 3-dialkylaminomethyl-1-azaanthraquinones and five 4-dialkylaminomethyl-1-azaanthraquinones were synthesized and evaluated in vitro cytotoxicity against four human can cer cell lines. The compounds retained much of their cytotoxic activity against the multi-drug-resistant cell line (KB-V-1) as shown by resistance index.

• Archives of Pharmacal Research
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• v.21 no.1
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• pp.73-75
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• 1998

In summary, six 4-substituted-1-azzanthraquinones were designed and synthesized using hetero Diels-Alder reaction as a key step. Although a great number of reaction conditions for benzylic bromination were examined, this step need to be improved for the efficient synthesis of the related analogues. 4-Bromomethyl-1-azzanthraquinone 6 may have potential for the treatment of tumors resistant to the doxorubicin. The compounds 9 and 10 containing the latent alkylating functionality may need further in depth biological evaluation. Work is in progress to design, synthesize, and evaluate additional compounds in this and related systems.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.351.2-351.2
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• 2002

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives on the model of doxorubicin(Dox). Dox is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of Quinone compounds like Dox. its use is limited because of systemic toxicities. primarily cardiotoxicity and myelosuppression. In this study. we describe the synthesis of benzoquinoxaline derivatives as DACA analogue. DACA has a neutral chromophore and acridine moiety and posions both topoisomerases I and ll with DNA intercalating activity. In order to delineate the SAR of benzoquinoxaline derivatives. an effcient sythetic rout to the target compounds without quinone group. Various attempted removal of quinone from benzoquinoxlinedione was unsuccessful. Diels-Alder rout applied for the synthesis of the target compounds will be discussed.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.507-512
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• 1998

In the course of developing novel antitumor intercalating agents. We synthesized 4-carbamoyloxymethyl-l-azaanthraquinones 7-12, incorporating the latent alkylating functi onality. These compounds were designed to explore the effect of substituent on the nitrogen of carbamate. The target compounds were prepared by hetero Diels-Alder reaction as a key step followed by functionalization of benzylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354; liver and MCF7; breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The compounds were less potent than doxorubicin against sensitive cell lines. However, the most active compound 12 was not cross-resistant with doxorubicin against KB-V-1.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.718-723
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• 1997

In the course of developing novel antitumor intercalating agents, we synthesized 3- carbamoyloxymethyl-azaanthraquinones 6-12, incorporating the latent alkylating functionality. These compounds were designed to explore the effect of heteroatom incorporation into anthraquinone chromophore and the effect of the incorporation of the latent alkylating functionality. The derivatives were prepared by hetero Diels-Alder reaction as a key step followed by functionality of allylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354: liver and MCF7: breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The derivatives were 10 to 100-fold less potent than doxorubicin against sensitive cell lines. However, they were marginally cross-resistant with doxorubicin against KB-V-1.