Nitrosoureas Modes of Action and Perspectives in the Use of Hormone Receptor Affine Carrier Molecules

Eisenbrand, Gerhard; Berger, Martin R.; Brix, H. P.; Fischer, J.; Mühlbauer, Karl; Nowrousian, Mohammad R.; Przybilski, M.; Schneider, Martin; Stahl, Wilhelm; Tang, Weici; Zelezny, Otto; Zeller, W. J.

doi:10.3109/02841868909111248

Cited by 13 publications

(2 citation statements)

References 27 publications

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“…The discovery of steroid hormone receptors and hormone responsiveness in a series of human tumors [7][8][9][10] offers the opportunity for targeting using drug-hormone conjugates [11][12][13][14][15]. The initial approach used for the design of complex molecules, comprising a nitrogen mustard and a steroidal skeleton, was based on the concept that the steroidal part would act as a 'biological platform' enabling the alkylating moiety to approach its site of action by altering its physicochemical properties (e.g.…”

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confidence: 99%

Structure–antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid: a comparative study

et al. 2007

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This study was designed as a rational continuation of our research regarding the functional requirements essential for the antileukemic activity of compounds comprising an alkylating moiety and a modified steroid. The steroidal esteric derivatives of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid were tested on leukemias P388 and L1210 in vivo and in normal human lymphocytes in vitro. Among them the B-lactamic steroidal esters proved more potent antileukemic agents than the 7-oxidized and those with a simple B-ring, but not more effective inducers of DNA damage and cell cycle arrest in vitro. We speculate that these results indicate a different mechanism of action induced by the lactamized B steroidal ring, in comparison to the 7-keto or the D-lactamic groups, which involves the interaction of the -NHCO- moiety with cellularcomponents essential for tumor growth. 4-Methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid proved a more proper module for the B-lactams than chlorambucil and phenyl acetic acid's nitrogen mustard probably because the esteric bond is less cleaved by the esterases, resulting in an increased concentration of the drug in the vinicity of the target site essential for an antineoplasmatic response.

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confidence: 99%

Structure–antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid: a comparative study

et al. 2007

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“…In order to increase the anti-neoplastic effects and reduce toxic effects on normal cells, attempts have been made to administer cancer chemotherapeutic agents linked to carriers like antibodies, liposomes, hormones and other macromolecules (Eisenbrand et al, 1989;Gregoriadis, 1976a,b;Hurwitz et al, 1975;Kaneko, 1981;Morgan et al, 1989;Rao et al, 1989;Trouet et al, 1972). A major problem in vivo has been the rapid clearance of such complexes from the bloodstream because they are recognised as foreign material by cells of the reticulo-endothelial system in the liver and the spleen.…”

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confidence: 99%

Low density lipoprotein for delivery of a water-insoluble alkylating agent to malignant cells. In vitro and in vivo studies of a drug-lipoprotein complex

Vitols

Söderberg-Reid²,

Masquelier³

et al. 1990

Br J Cancer

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Summary Previous studies have shown that human leukaemic cells and certain tumour tissues have a higher receptor-mediated uptake of low density lipoprotein (LDL) than the corresponding normal cells or tissues. LDL has therefore been proposed as a carrier for anti-cancer agents. In the current study, a water-insoluble mitoclomine derivative (WB 4291) was incorporated into LDL. The WB 4291 -LDL complex contained about 1,500 drug molecules per LDL particle and showed receptor-mediated toxicity in vitro as judged from the difference in growth inhibitory effect on normal and mutant (LDL-receptor-negative) cultured Chinese hamster ovary cells. However, cellular drug uptake did not exclusively occur by the receptor pathway since mutant cells were also affected to some extent. The LDL part of the complex had the same plasma clearance and organ distribution as native LDL after i.v. injection in mice and rabbits.

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Experiments on the Carcinogenic Potential of Antineoplastic Agents

Berger

1995

Late Sequelae in Oncology

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Nitrosoureas Modes of Action and Perspectives in the Use of Hormone Receptor Affine Carrier Molecules

Cited by 13 publications

References 27 publications

Structure–antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid: a comparative study

Structure–antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid: a comparative study

Low density lipoprotein for delivery of a water-insoluble alkylating agent to malignant cells. In vitro and in vivo studies of a drug-lipoprotein complex

Experiments on the Carcinogenic Potential of Antineoplastic Agents

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