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Titolo:
Cytotoxic activity of several unrelated drugs on L1210 mouse leukemic cellsublines with P-glycoprotein (PGP) mediated multidrug resistance (MDR) phenotype. A QSAR study
Autore:
Breier, A; Drobna, Z; Docolomansky, P; Barancik, M;
Indirizzi:
Slovak Acad Sci, Inst Mol Physiol & Genet, Bratislava 83334, Slovakia Slovak Acad Sci Bratislava Slovakia 83334 et, Bratislava 83334, Slovakia Slovak Acad Sci, Heart Res Inst, Bratislava 83334, Slovakia Slovak Acad Sci Bratislava Slovakia 83334 st, Bratislava 83334, Slovakia
Titolo Testata:
NEOPLASMA
fascicolo: 2, volume: 47, anno: 2000,
pagine: 100 - 106
SICI:
0028-2685(2000)47:2<100:CAOSUD>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSPORT; REVERSAL; VINCRISTINE; LINE;
Keywords:
P-glycoprotein; multidrug resistance; L1210 leukemic cell lines; cytostatic drugs; QSAR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Breier, A Slovak Acad Sci, Inst Mol Physiol & Genet, Vlarska 5, Bratislava83334, Slovakia Slovak Acad Sci Vlarska 5 Bratislava Slovakia 83334 4, Slovakia
Citazione:
A. Breier et al., "Cytotoxic activity of several unrelated drugs on L1210 mouse leukemic cellsublines with P-glycoprotein (PGP) mediated multidrug resistance (MDR) phenotype. A QSAR study", NEOPLASMA, 47(2), 2000, pp. 100-106

Abstract

L1210/VCR-1 and L1210/VCR-2 cell lines are multidrug resistant (MDR) sublines obtained by adaptation of mouse leukemic cell line L1210 to vincristineand, the development of MDR in these cell lines has been found to be associated with an overexpression of P-glycoprotein (PGP). In the present work we studied the relationship between the structure of 15 cytotoxic active substances (drugs) and their cytotoxicities on L1210/VCR-1 and L1210/VCR-2 resistant cell lines. The resistance of these MDR cells to the respective drugs was expressed as the ratio of IC50 Values obtained for resistant and sensitive cells. These values of resistance were correlated with the following physico-chemical constants of the test substances. binding energy, E-bind; total energy of the molecule, E-sum; aromaticity, K-pi; molecular weight, M-w; acidobasic constant, pK(a); partition coefficient in water/octanol two phase system, log(p). It has been found that according to the cytotoxic effects the tested drugs may be divided into three groups: (i) drugs with higher cytotoxicity to the resistant cell lines as to sensitive cells (collateral hypersensitivity); (ii) drugs exhibiting approximately similar effects on sensitive and resistant cell lines; (iii) drugs with weaker cytotoxicity to resistant cells than to sensitive cells. No direct correlations with anyphysico-chemical constant described above could be established for cell resistance to the drug studied. However, resistance: values could be fitted by multiple exponential regression with all described physico-chemical constants implied as six independent variables. The fatter procedure made us to conclude that the ability of a drug to be a substrate for PGP is connected with its fulfilling the following criteria. (i) flexible structure of its molecule; (ii) molecular weight lower than similar to 1300 g/mol; (iii) nonprotonized character at pH 7.0.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:14:20