4-[3-(2-Nitro-1-imidazolyl)propylamino]-7-chloroquinoline hydrochloride (NLCQ-1), a novel bioreductive compound as a hypoxia-selective cytotoxin

Oncology Research
M V PapadopoulouW D Bloomer

Abstract

A novel weakly DNA-intercalative bioreductive compound. 4-[3-(2-nitro-1-imidazolyl)-propylamino]-7-chloroquinoline hydrochloride (NLCQ-1). has been synthesized and studied as a hypoxia-selective cytotoxin in vitro. NLCQ-1, which shares a similar structure with the DNA-intercalative antimalarial drug chloroquine, bound more strongly to DNA than the nonchlorinated analog NLQ-1 (4-[3-(2-nitro-1-imidazolyl)propylamino]-quinaldine hydrochloride). Thus, NLCQ-1 exhibited a C50 [concentration for 50% displacement of the ethidium bromide (EB) from a DNA-EB complex] of 44 microM, whereas a C50 value could not be reached for NLQ-1 up to 225 microM. NLCQ-1 demonstrated significant hypoxic selectivity in several rodent (V79, EMT6, SCCVII) or human (A549, OVCAR-3) tumor cell lines. Its potency as a hypoxic cytotoxin (expressed as the product of exposure time and concentration for 50% survival) ranged between 10 and 136 microM x h, for the cell lines tested, at 30 microM input concentration. Because uptake in all cell lines was similar, the differences in potency may reflect differences in the enzymatic profile or damage repair processes among the cell lines. In addition, however, the most striking feature of NLCQ-1 was that hypoxic selectivi...Continue Reading

Citations

Aug 9, 2008·Medicinal Research Reviews·Yu Chen, Longqin Hu
Nov 6, 2002·Journal of Experimental Therapeutics & Oncology·Maria V PapadopoulouMelinda G Hollingshead
Apr 26, 2003·Cancer Chemotherapy and Pharmacology·Joel M ReidMatthew M Ames
Aug 29, 2007·Radiation Research·Maria V PapadopoulouMelinda G Hollingshead
May 9, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Man Chin ChungLorena Blau
May 12, 2009·Anti-cancer Drugs·Maria V Papadopoulou, William D Bloomer
Jan 6, 2011·Basic & Clinical Pharmacology & Toxicology·Maria V PapadopoulouWilliam D Bloomer
Oct 20, 2009·European Journal of Pharmacology·V Raja Solomon, Hoyun Lee
Mar 24, 2007·International Journal of Antimicrobial Agents·Maria V PapadopoulouMichael R McNeil
Oct 26, 2011·Journal of Medicinal Chemistry·Maria V PapadopoulouEls Torreele

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