Antileukemic activity of homo-aza-steroidal esters of the isomers of N,N-bis(2-chloroethyl)aminocinnamic acid

Catsoulacos, P.; Camoutsis, Ch.; Pelecanou, M.

doi:10.1016/0223-5234(91)90203-y

Cited by 9 publications

(4 citation statements)

References 8 publications

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“…lipophilicity). Although researchers in the past have used this notion [16][17][18] to explain the antileukemic activity of such compounds, recently new molecules of this category which were designed to possess small but effective differences (e.g. a simple keto group on a specific position of the steroidal skeleton) proved that the observed significant differentiations on the antileukemic potency of these compounds could not be explained only on the basis of the change of the physicochemical parameters [19,20].…”

mentioning

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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“…137 The antitumor activity of the esters of lactamic steroids in which the p-N,N-bis(2-chloroethyl)aminophenoxyacetic acid is linked to the C 3 (ring D lactam) or C 17 (ring A lactam) position has been extensively reviewed by Catsoulacos and Catsoulacos. 138 Compound 39 displayed significantly higher cytostatic effects than dacarbazine, carmustine, and semustine, but lower in comparison to cisplatin against malignant melanoma in an in vitro screening. 57 In a comparative study, the D-homoaza androstane derivatives were found distinctly superior to the corresponding steroidal 17β-amido-esters of p-N,N-bis(2-chloroethyl)amino-phenylacetic acid and p-N,N-bis(2-chloroethyl)aminophenylbutyric acid when evaluated for acute toxicity in mice, in vivo antileukemic activity against P388 and L1210 murine leukemias, and in vitro antileukemic effect on human leukemia cell lines (K562, MOLT-4, ML-1).…”

Section: Steroid Alkylating Agent Hybrid Moleculesmentioning

confidence: 96%

“…In a comparative study, the D-homoaza androstane derivatives were found distinctly superior to the corresponding steroidal 17β-amido-esters of p - N , N -bis(2-chloroethyl)amino-phenylacetic acid and p - N , N -bis(2-chloroethyl)aminophenylbutyric acid when evaluated for acute toxicity in mice, in vivo antileukemic activity against P388 and L1210 murine leukemias, and in vitro antileukemic effect on human leukemia cell lines (K562, MOLT-4, ML-1) . D-Homoaza-steroidal esters of N , N -bis(2-chloroethyl)aminocinnamic acid have also been synthesized and evaluated for cytotoxic and antileukemic activities along with the study of their structure–anticancer activity relationships. , …”

Section: Medicinal Chemistry Of Cytotoxic Steroidsmentioning

confidence: 99%

Man-Made Cytotoxic Steroids: Exemplary Agents for Cancer Therapy

Bansal

Acharya

2014

Chem. Rev.

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“…5 Previous studies have demonstrated versatile designs for N-mustard agents based on naphthalimide, 6,7 (L)-Carnitine, 8 steroid derivatives, 9,10 tallimustine, 11 tetrapyrrole, 12 aromatic structures 13 (including nitroaniline, 14 aminocinnamic acid 15 ), imidazole derivatives, 16 and distamycin. 17 Alkylating agents are the largest class of anticancer agents and are cell-cycle nonspecific drugs that form highly reactive electrophilic species.…”

Section: Introductionmentioning

confidence: 99%

Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents

Bartzatt¹,

Donigan²

2006

AAPS PharmSciTech

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The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH 2 -) between 2 -N(CH 2 CH 2 Cl) 2 groups. These compounds were shown to have significant correlations and associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis, and self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs, and hierarchical classification showed that each homolog had great similarity to at least one other member of the series-as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2 and 3 (by number of methylene groups) from homologs 4, 5, and 6 as a group, and from homologs 7, 8, and 9 as a group. Discriminant analysis, K-means cluster analysis, and hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased, and index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific and beneficial clinical applications for each homolog and methods of administration.

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Antileukemic activity of homo-aza-steroidal esters of the isomers of N,N-bis(2-chloroethyl)aminocinnamic acid

Cited by 9 publications

References 8 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

Man-Made Cytotoxic Steroids: Exemplary Agents for Cancer Therapy

Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents

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