Aza and diaza bioisosteric anthracene-9,10-diones as antitumor agents

• Autorzy: Krapcho A. P. , Maresch M.J. , Hacker M.P. , Menta E. , Oliva A. , Giuliani F.C. , Spinelli S.
• Języki publikacji: EN

Abstrakty

EN

Synthetic routes to aza and diaza bioisosteres related to the anthracene-9,10-dione, mitoxantrone, have been developed. The antitumor properties of these chemotypes are compared with those exhibited by the corresponding carbocyclic analogues. The sensitivity of the expressed cytotoxicities on the position(s) of the nitrogen atom(s) are discussed in terms of potential cellular targets. Several analogues show potential for clinical evaluations.

Słowa kluczowe

EN

anthracene; DNA binding; aza anthracene; antitumour agent; diaza anthracene

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1995
• Tom: 42
• Numer: 4
• Opis fizyczny: p.427-432

Twórcy

autor

Krapcho A. P.

• University of Vermont, Burlington, VT 05405 USA

autor

Maresch M.J.

autor

Hacker M.P.

autor

Menta E.

autor

Oliva A.

autor

Giuliani F.C.

autor

Spinelli S.

Bibliografia

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• 2. Faulds, D., Balfour, J.A., Chrisp, P. & Langtry, H. D. (1991) Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 41,400-449.
• 3. Lown, J.W. (ed.) (1988) Bioactive molecules, anthracycline and anthracenedione-based anticancer agents; vol. 6, Elsevier, New York.
• 4. Krapcho, A.P., Landi, }.)., Jr., Hacker, MP. & McCormack, J.J. (1985) Synthesis and antineo­plastic evaluations of 5,8-bis[(aminoalkyl)- aminol-l-aza-anthracene-9,10-diones. J. Med. Chem. 28, 1124-1126, and references cited therein.
• 5. Krapcho, A.P., Petry, M.E., Landi, J.J., Jr., Stallman, J., Polsenberg, J.F., Hacker, M.P., Spinelli, S., Oliva, A., Di Domenico, R. & Menta, E. (1993) The synthesis of 6,9-difluorobenzo- [g]quinoline-5,10-dione. Displacements of the fluorides by diamines which lead to 6,9- bis[(aminoalkyl)amino]benzo[g]quinoline-5,10 -diones.}. Heterocyclic Chem. 30,1565-1569.
• 6. Krapcho, A.P., Petry, M.E., Getahun, Z., Landi, J.J., Jr., Stallman, J., Polsenberg, J.F., Gallagher, C.E., Maresch, M., Hacker, M.P, Giuliani, F.C., Beggiolin, G., Pezzoni, G., Menta, E., Manzotti, C., Oliva, A., Spinelli, S. & Tognella, S. (1994) 6,9-Bis[(aminoalkyl)amino]benzo[g]isoquino- line-5,10-diones. A novel class of chromophore modified antitumor anthracene-9,10-diones: synthesis and antitumor evaluations. J. Med. Chem. 37,828-837.
• 7. Krapcho, A.P., Maresch, M., Helgason, A.L., Rosner, K.E., Hacker, M.P., Spinelli, S., Menta, E. & Oliva, A. (1993) The synthesis of 6,9-bis- I(aminoalkyl)amino] substituted benzo- [glquinoxaline-, benzo[g]quinazoline- and benzo[g]phthalazine-5,10-diones via regio- specific displacements. J. Heterocyclic Chem. 30, 1597-1606.
• 8. Zwelling, L.A., Mayes, J., Altschuler, E., Satitunwaycha, P., Tritton, T.R. & Hacker, M.P. (1993) Activity of two novel anthracene--9,10-diones against human leukemia cells containing intercalator-sensitive or -resistant forms of topoisomerase II. Biochem. Pharmacol 46,265-271.