Targeting of mitochondria by 10-N-alkyl acridine orange analogues: role of alkyl chain length in determining cellular uptake and localization.
10-N-Nonyl acridine orange (NAO) is used as a mitochondrial probe because of its high affinity for cardiolipin (CL). Targeting of NAO may also depend on mitochondrial membrane potential. As the nonyl group has been considered essential for targeting, a systematic study of alkyl chain length was undertaken; three analogues (10-methyl-, 10-hexyl-, and 10-hexadecyl-acridine orange) were synthesized and their properties studied in phospholipid monolayers and breast cancer cells. The shortest and longest alkyl chains reduced targeting, whereas the hexyl group was superior to the nonyl group, allowing very clear and specific targeting to mitochondria at concentrations of 20-100 nM, where no evidence of toxicity was apparent. Additional studies in wild-type and cardiolipin-deficient yeast cells suggested that cellular binding was not absolutely dependent upon cardiolipin.
Department of Radiation Oncology, School of Medicine (BRB-324), Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4942, USA.
Myriam E
ME
Rodriguez
Kashif
K
Azizuddin
Ping
P
Zhang
Song-mao
SM
Chiu
Minh
M
Lam
Malcolm E
ME
Kenney
Clemens
C
Burda
Nancy L
NL
Oleinick
D000165:Acridine Orange / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D002308:Cardiolipins / Q000378:metabolism; D045744:Cell Line, Tumor; D002477:Cells / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D002308:Cardiolipins; D005456:Fluorescent Dyes; D000165:Acridine Orange