“Triple” mutual prodrug based on 2-methoxyestradiol: synthesis and biotesting in vitro
Ester of the tubulin ligand, 2-methoxyestradiol, with two molecules of DNA alkylating agent chlorambucil was proposed as a “triple” mutual prodrug for blocking rapid metabolism of the initial steroid. The target conjugate was synthesized via the Steglich esterification. The biotesting results demons...
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| Veröffentlicht in: | Russian chemical bulletin 2020-03, Vol.69 (3), p.558-562 |
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| container_title | Russian chemical bulletin |
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| creator | Lavrushkina, E. A. Shibilev, V. M. Zefirov, N. A. Shevtsova, E. F. Shevtsov, P. N. Kuznetsov, S. A. Zefirova, O. N. |
| description | Ester of the tubulin ligand, 2-methoxyestradiol, with two molecules of DNA alkylating agent chlorambucil was proposed as a “triple” mutual prodrug for blocking rapid metabolism of the initial steroid. The target conjugate was synthesized
via
the Steglich esterification. The biotesting results demonstrate a very low cytotoxicity to cancer and conditionally normal cells (EC
50
~100 μmol L
−1
), a weak inhibition of the cell growth (A549: 20%/48 h), no stimulation of apoptosis, and no influence on the microtubule morphology of human lung carcinoma A549 cells and the ability to increase the rate of microtubule assembling. The sharp distinction of these properties from those for the initial 2-methoxyestradiol and chlorambucil molecules indicates that the synthesized prodrug is stable
in vitro
and demonstrates an expediency of its further testing
in vivo
. |
| doi_str_mv | 10.1007/s11172-020-2798-3 |
| format | Article |
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via
the Steglich esterification. The biotesting results demonstrate a very low cytotoxicity to cancer and conditionally normal cells (EC
50
~100 μmol L
−1
), a weak inhibition of the cell growth (A549: 20%/48 h), no stimulation of apoptosis, and no influence on the microtubule morphology of human lung carcinoma A549 cells and the ability to increase the rate of microtubule assembling. The sharp distinction of these properties from those for the initial 2-methoxyestradiol and chlorambucil molecules indicates that the synthesized prodrug is stable
in vitro
and demonstrates an expediency of its further testing
in vivo
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via
the Steglich esterification. The biotesting results demonstrate a very low cytotoxicity to cancer and conditionally normal cells (EC
50
~100 μmol L
−1
), a weak inhibition of the cell growth (A549: 20%/48 h), no stimulation of apoptosis, and no influence on the microtubule morphology of human lung carcinoma A549 cells and the ability to increase the rate of microtubule assembling. The sharp distinction of these properties from those for the initial 2-methoxyestradiol and chlorambucil molecules indicates that the synthesized prodrug is stable
in vitro
and demonstrates an expediency of its further testing
in vivo
.</description><subject>Alkylation</subject><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Cancer</subject><subject>Chemical synthesis</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chemistry/Food Science</subject><subject>Esterification</subject><subject>Full Articles</subject><subject>In vivo methods and tests</subject><subject>Inorganic Chemistry</subject><subject>Morphology</subject><subject>Organic Chemistry</subject><subject>Steroids</subject><subject>Toxicity</subject><issn>1066-5285</issn><issn>1573-9171</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1UMtOwzAQtBBIlMIHcLPE2eB1EtvhhipeUiUu5cLFihMndZXGxU4QvfVD4Of6JbgKEidOs6udmR0NQpdAr4FScRMAQDBCGSVM5JIkR2gCmUhIDgKO40w5JxmT2Sk6C2FFKWVSygl62---Ft5uWrPffeP10A9FizfeVX5osC6CqbDrMCNr0y_d59aE3heVde0tDtuuX5pgAy66Cmvr-ni0XYNthz9s7905OqmLNpiLX5yi14f7xeyJzF8en2d3c1ImwHsijUlLnXBacV1zwUseo4GMWy4rfYAsA5qaWvMyh7qmtI5rpiGVVICWyRRdjb4x9vsQQ6iVG3wXXyqWSCGAiSyNLBhZpXcheFOrjbfrwm8VUHWoUI0VqlihOlSokqhhoyZEbtcY_-f8v-gHDZ92Mg</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Lavrushkina, E. A.</creator><creator>Shibilev, V. M.</creator><creator>Zefirov, N. A.</creator><creator>Shevtsova, E. F.</creator><creator>Shevtsov, P. N.</creator><creator>Kuznetsov, S. A.</creator><creator>Zefirova, O. N.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20200301</creationdate><title>“Triple” mutual prodrug based on 2-methoxyestradiol: synthesis and biotesting in vitro</title><author>Lavrushkina, E. A. ; Shibilev, V. M. ; Zefirov, N. A. ; Shevtsova, E. F. ; Shevtsov, P. N. ; Kuznetsov, S. A. ; Zefirova, O. N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c316t-8ee4cb360d6bf676c602818d6b98dbd6b955104efb6c91ff00f1045b148071b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alkylation</topic><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Cancer</topic><topic>Chemical synthesis</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chemistry/Food Science</topic><topic>Esterification</topic><topic>Full Articles</topic><topic>In vivo methods and tests</topic><topic>Inorganic Chemistry</topic><topic>Morphology</topic><topic>Organic Chemistry</topic><topic>Steroids</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lavrushkina, E. A.</creatorcontrib><creatorcontrib>Shibilev, V. M.</creatorcontrib><creatorcontrib>Zefirov, N. A.</creatorcontrib><creatorcontrib>Shevtsova, E. F.</creatorcontrib><creatorcontrib>Shevtsov, P. N.</creatorcontrib><creatorcontrib>Kuznetsov, S. A.</creatorcontrib><creatorcontrib>Zefirova, O. N.</creatorcontrib><collection>CrossRef</collection><jtitle>Russian chemical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lavrushkina, E. A.</au><au>Shibilev, V. M.</au><au>Zefirov, N. A.</au><au>Shevtsova, E. F.</au><au>Shevtsov, P. N.</au><au>Kuznetsov, S. A.</au><au>Zefirova, O. N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>“Triple” mutual prodrug based on 2-methoxyestradiol: synthesis and biotesting in vitro</atitle><jtitle>Russian chemical bulletin</jtitle><stitle>Russ Chem Bull</stitle><date>2020-03-01</date><risdate>2020</risdate><volume>69</volume><issue>3</issue><spage>558</spage><epage>562</epage><pages>558-562</pages><issn>1066-5285</issn><eissn>1573-9171</eissn><abstract>Ester of the tubulin ligand, 2-methoxyestradiol, with two molecules of DNA alkylating agent chlorambucil was proposed as a “triple” mutual prodrug for blocking rapid metabolism of the initial steroid. The target conjugate was synthesized
via
the Steglich esterification. The biotesting results demonstrate a very low cytotoxicity to cancer and conditionally normal cells (EC
50
~100 μmol L
−1
), a weak inhibition of the cell growth (A549: 20%/48 h), no stimulation of apoptosis, and no influence on the microtubule morphology of human lung carcinoma A549 cells and the ability to increase the rate of microtubule assembling. The sharp distinction of these properties from those for the initial 2-methoxyestradiol and chlorambucil molecules indicates that the synthesized prodrug is stable
in vitro
and demonstrates an expediency of its further testing
in vivo
.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s11172-020-2798-3</doi><tpages>5</tpages></addata></record> |
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| language | eng |
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| subjects | Alkylation Apoptosis Biocompatibility Cancer Chemical synthesis Chemistry Chemistry and Materials Science Chemistry/Food Science Esterification Full Articles In vivo methods and tests Inorganic Chemistry Morphology Organic Chemistry Steroids Toxicity |
| title | “Triple” mutual prodrug based on 2-methoxyestradiol: synthesis and biotesting in vitro |
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