Synthesis of novel 17-(5'-iodo)triazolyl-3-methoxyestrane epimers via Cu(I)-catalyzed azide-alkyne cycloadditon, and an evaluation of their cytotoxic activity in vitro.
The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 3-methoxyestrane 17α- and 17β-azide epimers (3 and 5) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-f and 11a-f). If the Ph3P in the classical CuAAC process was replaced by Et3N, the formation of small quantities of 5-iodotriazoles (9a-f and 11a-f) was observed. For the preparation of 5-iodo-1,2,3-triazoles (9a-f and 11a-f), an improved method was developed, directly from steroidal azides and terminal alkynes, in reactions mediated by CuI and ICl as iodinating agents. The antiproliferative activities of the structurally related triazoles were determined in vitro with the microculture tetrazolium assay on six malignant human cell lines of gynecological origin (HeLa, A2780, MCF7, MDA-MB-231, MDA-MB-361 and T47D). X-ray analysis revealed the presence of the iodo substituent on the 1,2,3-triazole ring.
Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary. Electronic address: schneider@chem.u-szeged.hu.
Gyula
G
Schneider
Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
Tamás
T
Görbe
Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
Erzsébet
E
Mernyák
Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
János
J
Wölfling
Institute of Organic Chemistry, Research Center of Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1025 Budapest, Hungary.
Tamás
T
Holczbauer
Institute of Organic Chemistry, Research Center of Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1025 Budapest, Hungary.
Mátyás
M
Czugler
Institute of Chemistry, Eötvös Lóránd University, Pázmány Péter sétány 1/A, H-1117 Budapest, Hungary.
Pál
P
Sohár
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u.6, H-6720 Szeged, Hungary.
Renáta
R
Minorics
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u.6, H-6720 Szeged, Hungary. Electronic address: zupko@pharm.u-szeged.hu.
István
I
Zupkó
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004962:Estranes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006847:Hydrocarbons, Iodinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells
D000970:Antineoplastic Agents; D003603:Cytotoxins; D004962:Estranes; D006847:Hydrocarbons, Iodinated; D003300:Copper
1,3-Dipolar cycloaddition; Cytotoxic activity; Iodotriazoles; X-ray analysis