Tertiary amine N-oxides as bioreductive drugs: DACA N-oxide, nitracrine N-oxide and AQ4N

British Journal of Cancer

Volumn 74, Issue SUPPL. XXVII, 1996, Pages

  Wilson, W R ^a   Denny, W A ^a   Pullen, S M ^a   Thompson, K M ^a   Li, A E ^a   Patterson, L H ^b   Lee, H H ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b DE MONTFORT UNIVERSITY   (United Kingdom)

Author keywords

AQ4N; Bioreductive drug; DACA; DMXAA; Hypoxia; Topoisomerase inhibitor

Indexed keywords

1 (2 BROMOETHYLAMINO) 3 (2 NITRO 1 IMIDAZOLYL) 2 PROPANOL; 5,6 DIMETHYLXANTHENONE 4 ACETIC ACID; AMINE OXIDE; ANTINEOPLASTIC AGENT; N (2 DIMETHYLAMINOETHYL) 4 ACRIDINECARBOXAMIDE; NITRACRINE; PRODRUG; 1,4 BIS[[2 (DIMETHYLAMINO N OXIDE)ETHYL]AMINO] 5,8 DIHYDROXYANTHRAQUINONE; 5,6 DIMETHYLXANTHENONEACETIC ACID; 5,6-DIMETHYLXANTHENONEACETIC ACID; ACRIDINE DERIVATIVE; ANTHRAQUINONE DERIVATIVE; C 684; DRUG DERIVATIVE; INTERCALATING AGENT; XANTHENE DERIVATIVE; XANTHONE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; BREAST TUMOR; CELL CULTURE; CELL CYCLE; CELL KILLING; CONFERENCE PAPER; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACTIVATION; DRUG ACTIVITY; DRUG DNA BINDING; HYPOXIA; INTRAPERITONEAL DRUG ADMINISTRATION; MOUSE; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RADIATION; REDUCTION; TUMOR BLOOD FLOW; ANIMAL; ARTICLE; CELL SURVIVAL; DRUG EFFECT; EXPERIMENTAL NEOPLASM; HUMAN; OXIDATION REDUCTION REACTION;

ACRIDINES; ANIMALS; ANTHRAQUINONES; ANTINEOPLASTIC AGENTS; CELL SURVIVAL; HUMANS; INTERCALATING AGENTS; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; NITRACRINE; OXIDATION-REDUCTION; PRODRUGS; XANTHENES; XANTHONES;

EID: 0029935930     PISSN: 00070920     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (16)

1. ATWELL GJ, REWCASTLE GW, BAGULEY GW AND DENNY WA. (1987). Potential antitumor agents. 50. In vivo solid tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide. J. Med. Chem., 30, 664-669.
2. CLIFFE S, TAYLOR ML, RUTLAND M, BAGULEY B, HILL RP AND WILSON WR. (1994). Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid. Int. J. Radiat. Oncol. Biol. Phys., 29, 373-377.
3. COLE S, PATTERSON LH, WILLIAMS CA, BOWLER JD, RALEIGH S AND STRATFORD IJ. The activity of AQ4N, a novel, bioreductively-activated cytotoxin against KHT, RIF-1 and SCCVII murine tumours in vivo. 9th International conference on chemical modifiers of Cancer Treatment, Oxford 22-26 August, 1995, (Abstract).
4. CRENSHAW JM, GRAVES DE AND DENNY WA. (1995). Interactions of acridine antitumour agents with DNA: binding energies and groove preferences. Biochemistry, 34, 13862-13867.
5. DENNY WA AND WILSON WR. (1986). Considerations for the design of nitrophenyl mustards as agents with selective toxicity for hypoxic tumour cells. J. Med. Chem., 29, 879-887.
6. FINLAY GJ AND BAGULEY BC. (1989). Selectivity of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide towards Lewis lung carcinoma and human tumour cell lines in vitro. Eur. J. Cancer Clin. Oncol., 25, 271-277.
7. FINLAY GJ, MARSHALL E, MATTHEWS JHL, PAUL KD AND BAGULEY BC. (1993). In vitro assessment of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide, a DNA-intercalating antitumour drug with reduced senstivity to multidrug resistance. Cancer Chemother. Pharmacol., 31, 401-406.
8. LEE HH, WILSON WR, FERRY DM, VAN ZIJL P, PULLEN SM AND DENNY WA. (1996). Hypoxia-selective antitumor agents. 13. Effects of acridine substitution on the hypoxia-selective cytotoxicity and metabolic reduction of the bis-bioreductive agent nitracine N-oxide. J. Med. Chem. (in press).
9. MCKEOWN SR, HEJMADI MV, MCINTYRE IA, MCALEER JJA AND PATTERSON LH. (1995). AQ4N: An alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo. Br. J. Cancer, 72, 76-81.
10. MOSELEN J, HAY M, DENNY WA AND WILSON WR. (1995). N-[2-(2-methyl-5-nitroimidazolyl)ethyl]-4-(2-nitroimidazolyl)-butanamide (NNB, NSC 639862), a bis-bioreductive agent with marked selective toxicity towards hypoxic cells. Cancer Res., 55, 574-580.
11. PALMER BD, VAN ZIJL P, DENNY WA AND WILSON WR. (1995). Reductive chemistry of the novel hypoxia-selective cytotoxin 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (SN 23862). J. Med. Chem., 38, 1229-1241.
12. PATTERSON LH. (1993). Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent. Cancer Metastasis Rev., 12, 119-134.
13. PATTERSON LH, CRAVEN MR, FISHER GR AND TEESDALE-SPITTLE P. (1995). Aliphatic amine N-oxides of DNA binding agents as bioreductive drugs. Oncol. Res., 6, 533-538.
14. THOMPSON LH, SALAZAR EP, BROOKMAN KW AND HOY CA. (1983). Hypersensitivity to cell killing and mutation induction by chemical carcinogens in an excision repair-deficient mutant of CHO cells. Mutation Res., 112, 329-344.
15. WILSON, WR, VAN ZIJL, P & DENNY. WA (1992). Bis-bioreductive agents as hypoxia-selective cytotoxins: nitracrine N-oxide. Int. J. Radiat. Oncol. Biol. Phys., 22, 693-696.
16. WILSON WR, VAN ZIJL P, FERRY DM, COOMBE SL, ANDERSON RF, LEE HH AND DENNY WA. (1994). Evidence that metabolic reduction of aliphatic N-oxides is an oxygen-inhibitable two-electron process. International Conference on Bioreductive Drug Activation, Lake Tahoe, CA, 16-19, August 1994 (abstract).