title: Synthesis and in vitro pharmacological evaluation of N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]-carboxamides on d-secoestrone scaffolds.
abstract: An efficient synthesis of several N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]carboxamides in the 13β- and 13α-d-secoestrone series is reported. Novel triazoles were synthesized via the Cu(I)-catalyzed azide-alkyne cycloaddition of steroidal alkynyl carboxamides and p-substituted benzyl azides. Each of the products was evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A431 and A2780). Some of them exhibited activities similar to those of the reference agent cisplatin. On change of the substitution pattern of the benzyl group of the azide, great differences in the cell growth-inhibitory properties were observed. The p-alkylbenzyl-substituted triazoles selectively exerted high cytostatic action against A2780 cells, with IC50 values of 1 µM. We investigated the potential inhibitory action exerted on the human 17β-HSD1 activity of the new secosteroids. Three triazoles effectively suppressed the estrone to 17β-estradiol conversion with IC50 values in low micromolar range.
authors.affiliation: a Department of Organic Chemistry , University of Szeged , Szeged , Hungary .
authors.forename: Johanna
authors.initials: J
authors.lastname: Szabó
authors.affiliation: a Department of Organic Chemistry , University of Szeged , Szeged , Hungary .
authors.forename: Ildikó
authors.initials: I
authors.lastname: Bacsa
authors.affiliation: a Department of Organic Chemistry , University of Szeged , Szeged , Hungary .
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.affiliation: a Department of Organic Chemistry , University of Szeged , Szeged , Hungary .
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.affiliation: b Department of Pharmacodynamics and Biopharmacy , University of Szeged , Szeged , Hungary .
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.affiliation: c Cereal Research Non-Profit Ltd. , Szeged , Hungary .
authors.forename: Mónika
authors.initials: M
authors.lastname: Varga
authors.affiliation: d 1st Department of Medicine , University of Szeged, Szeged , Hungary , and.
authors.forename: Bianka E
authors.initials: BE
authors.lastname: Herman
authors.affiliation: e Department of Obstetrics and Gynecology , University of Szeged , Szeged , Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Kalmár
authors.affiliation: d 1st Department of Medicine , University of Szeged, Szeged , Hungary , and.
authors.forename: Mihály
authors.initials: M
authors.lastname: Szécsi
authors.affiliation: a Department of Organic Chemistry , University of Szeged , Szeged , Hungary .
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004960:Estradiol Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001593:Benzyl Compounds; C000614206:D-secoestrone; D004791:Enzyme Inhibitors; C000614205:N-((1-benzyl-1,2,3-triazol-4-yl)methyl)carboxamide; D014230:Triazoles; D004970:Estrone; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human
keywords: 17β-HSD1 inhibition; A2780; Antiproliferative effect; azide–alkyne cycloaddition; steroid