PMID: 11933073Apr 5, 2002Paper

Quinoxaline 1,4-dioxides: hypoxia-selective therapeutic agents

Molecular Carcinogenesis
Mona Diab-AssefHala Gali-Muhtasib

Abstract

A problem that confronts clinicians in the treatment of cancer is the resistance of hypoxic tumors to chemotherapy and radiation therapy. Thus, the development of new drugs that are toxic to hypoxic cells found in solid tumors is an important objective for effective anticancer chemotherapy. We recently showed that the heterocyclic aromatic N-oxides, quinoxaline 1,4-dioxides (QdNOs), are cytotoxic to tumor cells cultured under hypoxia. In this study, we evaluated the hypoxia-selective toxicity of four diversely substituted QdNOs and determined their effect on the expression of hypoxia inducible factor (HIF) 1alpha in the human colon cancer cell line T-84. The various QdNOs were found to possess a 50- to 100-fold greater cytotoxicity to T-84 cells cultured under hypoxia compared with oxia. Interestingly, the hypoxia cytotoxicity ratio (HCR), the ratio of equitoxic concentrations of the drug under aerobic/anoxic conditions, was highly structure related and depended on the nature of the substituents on the QdNO heterocycle. The most cytotoxic 2-benzoyl-3-phenyl-6,7-dichloro derivative of QdNO (DCQ) was potent at a dose of 1 microM with an HCR of 100 and significantly reduced the levels of HIF-1alpha transcript and protein. The 2-be...Continue Reading

References

May 1, 1978·Antimicrobial Agents and Chemotherapy·W SuterF Knüsel
Apr 1, 1989·International Journal of Radiation Oncology, Biology, Physics·I J Stratford, M A Stephens
Jul 1, 1986·International Journal of Radiation Oncology, Biology, Physics·E M ZemanW W Lee
Feb 12, 1972·The Veterinary Record·T D Hennessey, J R Edwards
Apr 1, 1972·The Veterinary Record·B D Hoskin, P M Lyon
Jan 1, 1980·Biochemical Pharmacology·K A KennedyA C Sartorelli
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
May 12, 1995·Journal of Medicinal Chemistry·A MongeM González
Jan 1, 1994·International Journal of Radiation Biology·J M Brown, A J Giaccia

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Citations

Nov 13, 2004·Cancer Chemotherapy and Pharmacology·Hala U Gali-MuhtasibMakhluf J Haddadin
Apr 11, 2007·Chemico-biological Interactions·Amaia AzquetaAdela López de Cerain
Apr 6, 2016·Frontiers in Pharmacology·Guyue ChengZonghui Yuan
May 23, 2015·Toxicology Mechanisms and Methods·Chongshan DaiXilong Xiao
Nov 17, 2007·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Joelle HaykalHala Gali-Muhtasib
Apr 7, 2018·Cancer Investigation·Alexander M ScherbakovAndrey E Shchekotikhin

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