Article

Synthesis and antiproliferative activity of some steroidal lactams.

Department of Chemistry, Guangxi Teachers Education University, Nanning 530001, China.
Steroids (impact factor: 2.83). 07/2011; 76(12):1346-50. DOI:10.1016/j.steroids.2011.06.013 pp.1346-50
Source: PubMed

ABSTRACT Using cholesterol as starting material, a series of 6-substituted-3-aza-A-homo-3-oxycholestanes and 6-substituted-4-aza-A-homo-3-oxycholestanes were synthesized by the oxidation, reduction, oximation, Beckman rearrangement and condensation reaction. These synthesized compounds displayed a distinct cytotoxicity against MGC 7901, HeLa and SMMC 7404 cancer cells. Our results revealed that the structures of functional groups at position-6 on the steroidal ring are crucial for the IC(50) value of antiproliferative activities of these compounds and the cytotoxic activity against MGC 7901 and SMMC 7404 cells was not significantly different between 4-N-lactams and 3-N-lactams when its 6-substituted group was a carbonyl or a hydroximino, but all 3-N-lactams showed a higher cytotoxicity against HeLa cells than 4-N-lactams. In particular, compounds 6, 8, 9 (IC(50)6: 6.5 μmol/L; 8: 7.7 μmol/L; 9: 5.6 μmol/L) were even more cytotoxic than cisplatin to HeLa cells (positive contrast, 10.1 μmol/L). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.

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    Article: Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro.
    Agnes Berényi, Renáta Minorics, Zoltán Iványi, Imre Ocsovszki, Eszter Ducza, Hubert Thole, Josef Messinger, János Wölfling, Gergő Mótyán, Erzsébet Mernyák, Eva Frank, Gyula Schneider, István Zupkó
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    ABSTRACT: An expanding body of evidence indicates the possible role of estrane derivatives as useful anticancer agents. The aim of this study was to describe the cytotoxic effects of 63 newly synthetized estrone-16-oxime ethers on human cancer cell lines (cervix carcinoma HeLa, breast carcinoma MCF7 and skin epidermoid carcinoma A431), studied by means of the MTT assay. Four of the most promising compounds were selected for participation in additional experiments in order to characterize the mechanism of action, including cell cycle analysis, morphological study and the 5-bromo-2'-deoxyuridine incorporation assay. The cancer selectivity was tested on a noncancerous fibroblast cell line (MRC-5). Since apoptosis and cell cycle disturbance were observed, caspase-3 activities were further assayed for the two most effective agents. These estrone-16-oxime analogs activated caspase-3 and changed the mRNA level expression of endogenous factors regulating the G1 - S phase transition (retinoblastoma protein, CDK4 and p16). The repression of retinoblastoma protein was reinforced at a protein level too. These experimental data lead to the conclusion that estrone-16-oxime ethers may be regarded as potential starting structures for the design of novel anticancer agents.
    Steroids 01/2013; 78:69-78. · 2.83 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

4-N-lactams
 
6-substituted group
 
6-substituted-3-aza-A-homo-3-oxycholestanes
 
6-substituted-4-aza-A-homo-3-oxycholestanes
 
antiproliferative activities
 
Beckman rearrangement
 
carbonyl
 
cisplatin
 
compounds
 
compounds 6
 
condensation reaction
 
cytotoxic activity
 
functional groups
 
novel chemotherapeutic drugs
 
oxidation
 
oximation
 
positive contrast
 
SMMC 7404 cancer cells
 
synthesized compounds
 

Yanmin Huang