Fluorescent cationic probes for nuclei of living cells: why are they selective? A quantitative structure-activity relations analysis

被引:104
作者
Horobin, Richard W. [1 ]
Stockert, Juan C. [2 ]
Rashid-Doubell, Fiza [3 ]
机构
[1] Univ Glasgow, Inst Biomed & Life Sci, Div Neurosci & Biomed Syst, Glasgow G12 8QQ, Lanark, Scotland
[2] Univ Autonoma Madrid, Dept Biol, E-28049 Madrid, Spain
[3] Univ Oxford, John Radcliffe Hosp, Dept Obstet & Gynaecol, Oxford OX3 9DU, England
关键词
DNA; Nuclear fluorescent probe; QSAR; Vital staining mechanism;
D O I
10.1007/s00418-006-0156-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Selectivity of nuclear probes is controlled by competitive accumulation of the probe by cellular organelles as well as the high affinity for nucleic acids. Physicochemical features of probes which favor nucleic acid binding include cationic character and a planar aromatic system above a minimum size. Features of probes which permit entry into cells are low protein and lipid binding. Features which reduce accumulation in non-nuclear sites include high base strength and hydrophilicity of the cation. The overall quantitative structure-activity ( QSAR) model specifying nuclear accumulation may be expressed as follows: CBN < 40; 8 > log P(neutral species) > 0; AI < 8; Z > 0; -5 < log P(cation) < 0; pK(a) > 10; LCF > 17; LCF/CBN > 0.70 ( where CBN is the conjugated bond number, log P(x) the logarithm of the water-octanol partition coefficient of species x, AI the amphilicity index, Z the electric charge, pK(a) the negative logarithm of the equilibrium constant for the free base-protonated base reaction, and LCF the largest conjugated fragment). Preliminary applications of the QSAR model-to the selection of anticancer drugs, minimization of dye and drug toxicity and the designed synthesis of fluorescent probes-are outlined.
引用
收藏
页码:165 / 175
页数:11
相关论文
共 49 条
[1]   Correlation of basicity and antiseptic action in an acridine series [J].
Albert, A ;
Rubbo, SD ;
Goldacre, R .
NATURE, 1941, 147 :332-333
[2]  
Albert A, 1966, The Acridines: their Preparation, Physical, Chemical, and Biological Properties and Uses, V2nd
[3]  
Anliker Q.R., 1986, TOXIC HAZARD ASSESSM, P166
[4]  
[Anonymous], ADV COLOUR SCI TECHN
[5]  
[Anonymous], 1990, SIGMA ALDRICH HDB ST
[6]  
[Anonymous], 1979, SELECTIVE TOXICITY P
[7]   The induction of apoptosis by a positively charged methylene blue derivative [J].
Ball, DJ ;
Luo, Y ;
Kessel, D ;
Griffiths, J ;
Brown, SB ;
Vernon, DI .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1998, 42 (02) :159-163
[8]   A NEW ASSAY FOR CELL-DEATH [J].
BELETSKY, IP ;
UMANSKY, SR .
JOURNAL OF IMMUNOLOGICAL METHODS, 1990, 134 (02) :201-205
[9]  
BUNTING JW, 1973, CAN J CHEM, V51, P1965, DOI 10.1139/v73-294
[10]  
BUNTING JW, 1980, HETEROCYCLES, V14, P2015