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Evgenija A. Djurendić - One of the best experts on this subject based on the ideXlab platform.
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New A-homo lactam D-homo lactone Androstane Derivative: Synthesis and evaluation of cytotoxic and anti-inflammatory activities in vitro.
Steroids, 2020Co-Authors: Marina P. Savić, Dušan Dj. Škorić, Ivana Kuzminac, Dimitar Jakimov, Vesna Kojić, Lucie Rárová, Miroslav Strnad, Evgenija A. DjurendićAbstract:Abstract This paper describes the synthesis of a new A-homo lactam D-homo lactone Androstane Derivative from dehydroepiandrosterone. To evaluate the impact of the introduction of nitrogen in the parental scaffold on biological activity, a new Androstane enamide-type lactam Derivative was prepared and characterized. The new compound as well as starting compounds were screened for cytotoxic, anti-angiogenic and anti-inflammatory activities using several human cancer cell lines (MCF-7, MDA-MB-231, PC3, CEM, G-361, HeLa), endothelial (HUVEC) and non-tumour (MRC-5 and BJ) cell lines. Strong cytotoxic and anti-inflammatory activity with a broad therapeutical window was demonstrated by the A-homo lactam D-homo lactone Androstane Derivative. The induction of apoptosis in treated PC3 cultures was confirmed using apoptotic morphology screening and a fluorescent double-staining method. New A-homo lactam D-homo lactone Androstane Derivative induced apoptosis more than the tested reference compounds, Formestane and Doxorubicin. An in silico ADME analysis showed that the compounds possess drug-like properties.
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Synthesis, Structural Analysis and Cytotoxic Activity of Novel A- and B-Modified d-Homo Lactone Androstane Derivative
Journal of Chemical Crystallography, 2016Co-Authors: Marina P. Savić, Olivera R. Klisurić, Katarina M. Penov Gaši, Dimitar S. Jakimov, Marija N. Sakač, Evgenija A. DjurendićAbstract:The d -homo Androstane lactone 3β-hydroxy-17-oxa- d -homoandrost-5-en-16-one ( I) was transformed through intermediate compounds 17-oxa- d -homoandrost-4-ene-3,16-dione ( II) and/or 17-oxa- d -homoandrost-4-ene-3,6,16-trione ( III) to 3( E ),6( E )-dihydroximino-17-oxa- d -homoandrost-4-en-16-one ( IV ), which was characterized using analytical and spectral data. Compound IV was examined by X-ray crystallography, IR and NMR spectroscopy. Compound IV crystallized in a monoclinic system with a P2_1 space group. The dimensions of the unit cell are: a = 11.2815(5) Å; b = 13.1512(4) Å; c = 13.7145(8) Å; β = 110.890(5)°. The asymmetric unit cell consists of two symmetrically independent molecules ( A and B ) of 3( E ),6( E )-dihydroximino-17-oxa- d -homoandrost-4-en-16-one and one methanol molecule. In the molecular structure of compound IV , two molecules in the asymmetric unit are connected by O–H···N hydrogen bonds, while the crystal packing of compound IV is predominantly organized by a dense network of O–H···O hydrogen bonds, mostly involving the O atom from the methanol molecule as donor or acceptor. Derivatives I–IV were screened for antitumor activity against six human cancer cell lines and one non-tumor cell line. Graphical Abstract The d -homo Androstane lactone (3β-hydroxy-17-oxa- d -homoandrost-5-en-16-one) I was transformed through intermediate compounds 17-oxa- d -homoandrost-4-ene-3,16-dione ( II) and/or 17-oxa- d -homoandrost-4-ene-3,6,16-trione ( III) to 3( E ),6( E )-dihydroximino-17-oxa- d -homoandrost-4-en-16-one ( IV ) which was characterized according to the analytical and spectral data. Compound IV was examined by X-ray crystallography, IR and NMR spectroscopy. Derivatives I–IV were screened for antitumor activity against six human cancer cell lines and one non-tumor cell line.
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Preselection of A- and B- modified d-homo lactone and d-seco Androstane Derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Strahinja Z. Kovačević, Marina P. Savić, Sanja O. Podunavac-kuzmanović, Lidija R. Jevrić, Vladimir R. Vukić, Evgenija A. DjurendićAbstract:Abstract The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d -homo lactone and d -seco Androstane Derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d -homo lactone and/or d -seco Androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- ( 3 ) and 6α,7α-epoxy-1,4-dien-3-one ( 24 ) d -homo lactone Androstane Derivatives, as well as 4-en-3-one ( 15 ) d -seco Androstane Derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer – abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d -homo lactone and d -seco Androstane Derivatives with antiproliferative activity against breast and prostate cancer cells.
Marina P. Savić - One of the best experts on this subject based on the ideXlab platform.
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New A-homo lactam D-homo lactone Androstane Derivative: Synthesis and evaluation of cytotoxic and anti-inflammatory activities in vitro.
Steroids, 2020Co-Authors: Marina P. Savić, Dušan Dj. Škorić, Ivana Kuzminac, Dimitar Jakimov, Vesna Kojić, Lucie Rárová, Miroslav Strnad, Evgenija A. DjurendićAbstract:Abstract This paper describes the synthesis of a new A-homo lactam D-homo lactone Androstane Derivative from dehydroepiandrosterone. To evaluate the impact of the introduction of nitrogen in the parental scaffold on biological activity, a new Androstane enamide-type lactam Derivative was prepared and characterized. The new compound as well as starting compounds were screened for cytotoxic, anti-angiogenic and anti-inflammatory activities using several human cancer cell lines (MCF-7, MDA-MB-231, PC3, CEM, G-361, HeLa), endothelial (HUVEC) and non-tumour (MRC-5 and BJ) cell lines. Strong cytotoxic and anti-inflammatory activity with a broad therapeutical window was demonstrated by the A-homo lactam D-homo lactone Androstane Derivative. The induction of apoptosis in treated PC3 cultures was confirmed using apoptotic morphology screening and a fluorescent double-staining method. New A-homo lactam D-homo lactone Androstane Derivative induced apoptosis more than the tested reference compounds, Formestane and Doxorubicin. An in silico ADME analysis showed that the compounds possess drug-like properties.
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Synthesis, Structural Analysis and Cytotoxic Activity of Novel A- and B-Modified d-Homo Lactone Androstane Derivative
Journal of Chemical Crystallography, 2016Co-Authors: Marina P. Savić, Olivera R. Klisurić, Katarina M. Penov Gaši, Dimitar S. Jakimov, Marija N. Sakač, Evgenija A. DjurendićAbstract:The d -homo Androstane lactone 3β-hydroxy-17-oxa- d -homoandrost-5-en-16-one ( I) was transformed through intermediate compounds 17-oxa- d -homoandrost-4-ene-3,16-dione ( II) and/or 17-oxa- d -homoandrost-4-ene-3,6,16-trione ( III) to 3( E ),6( E )-dihydroximino-17-oxa- d -homoandrost-4-en-16-one ( IV ), which was characterized using analytical and spectral data. Compound IV was examined by X-ray crystallography, IR and NMR spectroscopy. Compound IV crystallized in a monoclinic system with a P2_1 space group. The dimensions of the unit cell are: a = 11.2815(5) Å; b = 13.1512(4) Å; c = 13.7145(8) Å; β = 110.890(5)°. The asymmetric unit cell consists of two symmetrically independent molecules ( A and B ) of 3( E ),6( E )-dihydroximino-17-oxa- d -homoandrost-4-en-16-one and one methanol molecule. In the molecular structure of compound IV , two molecules in the asymmetric unit are connected by O–H···N hydrogen bonds, while the crystal packing of compound IV is predominantly organized by a dense network of O–H···O hydrogen bonds, mostly involving the O atom from the methanol molecule as donor or acceptor. Derivatives I–IV were screened for antitumor activity against six human cancer cell lines and one non-tumor cell line. Graphical Abstract The d -homo Androstane lactone (3β-hydroxy-17-oxa- d -homoandrost-5-en-16-one) I was transformed through intermediate compounds 17-oxa- d -homoandrost-4-ene-3,16-dione ( II) and/or 17-oxa- d -homoandrost-4-ene-3,6,16-trione ( III) to 3( E ),6( E )-dihydroximino-17-oxa- d -homoandrost-4-en-16-one ( IV ) which was characterized according to the analytical and spectral data. Compound IV was examined by X-ray crystallography, IR and NMR spectroscopy. Derivatives I–IV were screened for antitumor activity against six human cancer cell lines and one non-tumor cell line.
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Preselection of A- and B- modified d-homo lactone and d-seco Androstane Derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Strahinja Z. Kovačević, Marina P. Savić, Sanja O. Podunavac-kuzmanović, Lidija R. Jevrić, Vladimir R. Vukić, Evgenija A. DjurendićAbstract:Abstract The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d -homo lactone and d -seco Androstane Derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d -homo lactone and/or d -seco Androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- ( 3 ) and 6α,7α-epoxy-1,4-dien-3-one ( 24 ) d -homo lactone Androstane Derivatives, as well as 4-en-3-one ( 15 ) d -seco Androstane Derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer – abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d -homo lactone and d -seco Androstane Derivatives with antiproliferative activity against breast and prostate cancer cells.
Henry Chermette - One of the best experts on this subject based on the ideXlab platform.
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Study of Prepolymerization Complex Formation in the Synthesis of Steroid-Based Molecularly Imprinted Polymers
Analytical Chemistry, 2012Co-Authors: Corinne Sanglar, Tim Jansen, Marius C. Silaghi, Julien Mernier, Pierre Mignon, Henry ChermetteAbstract:The preparation of steroid-based molecularly imprinted polymers (MIPs) based upon noncovalent interaction is particularly suited for selective capture of steroid hormones in biological and environmental samples. The success of this method lies in the optimization of the interaction between steroids (template) and methacrylic acid (functional monomer) in the prepolymerization mixture. NMR techniques coupled with DFT calculations were used to evaluate the capacity of the methacrylic acid to bind a steroid for future applications. The Androstane Derivative steroids considered in the present study have two functional groups at C3 and C17, which may interact with the methacrylic acid. These can be hydroxyl or ketone groups. Experimental results show that the steroids can be divided in three groups corresponding to the ketone type at C3, the H-bond strength increasing with the number of double bonds. DFT calculations are in very good agreement with experimental results, showing increasing binding energy from no bonds, a single bond, and two double bond steroids. For steroids holding a hydroxyl group the binding energy obtained in the solvent model is comparable to the binding energy of single bond ketone steroids.
Lakshmanaswamy Rajkumar - One of the best experts on this subject based on the ideXlab platform.
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17α-Ethynyl-5α-Androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats
SAGE-Hindawi Access to Research, 1Co-Authors: Ahlem, Clarence N., Frincke, James M., White, Steven K., Reading, Christopher L., Trauger, Richard J., Lakshmanaswamy RajkumarAbstract:N-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female Lewis rats. We explored the antineoplastic activity of a synthetic Androstane Derivative, 17α-ethynyl-5α-Androstane-3α, 17β-diol (HE3235), as a single agent or in combination with docetaxel compared to tamoxifen, anastrazole, and docetaxel monotherapies against MNU-induced mammary tumors in female Lewis rats. Treatment with HE3235 alone rapidly reduced tumor burden, similar in effect to tamoxifen and anastrozole. The combination of HE3235 with docetaxel was more effective than any single agent, although without apparent toxicity. Only HE3235 or HE3235 plus docetaxel continued to suppress tumor growth after cessation of treatment. HE3235 treatment increased immunohistochemical markers of apoptosis and expression of proapoptotic genes and estrogen receptor beta and decreased expression of antiapoptotic genes, androgen receptor, and estrogen receptor alpha. These data warrant clinical investigation of HE3235 for breast cancer treatment
Rajkumar Lakshmanaswamy - One of the best experts on this subject based on the ideXlab platform.
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Research Article 17α-Ethynyl-5α-Androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats
2011Co-Authors: Richard J. Trauger, Rajkumar LakshmanaswamyAbstract:Copyright © 2011 Clarence N. Ahlem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. N-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female Lewis rats. We explored the antineoplastic activity of a synthetic Androstane Derivative, 17α-ethynyl-5α-Androstane-3α, 17β-diol (HE3235), as a single agent or in combination with docetaxel compared to tamoxifen, anastrazole, and docetaxel monotherapies against MNU-induced mammary tumors in female Lewis rats. Treatment with HE3235 alone rapidly reduced tumor burden, similar in effect to tamoxifen and anastrozole. The combination of HE3235 with docetaxel was more effective than any single agent, although without apparent toxicity. Only HE3235 or HE3235 plus docetaxel continued to suppress tumor growth after cessation of treatment. HE3235 treatment increased immunohistochemical markers of apoptosis and expression of proapoptotic genes and estrogen receptor beta and decreased expression of antiapoptotic genes, androgen receptor, and estrogen receptor alpha. These data warrant clinical investigation of HE3235 for breast cancer treatment. 1
