Synthesis, structural analysis and cytotoxic activity of novel A- and B-modified d-homo lactone androstane derivative

Abstract

© 2016 Springer Science+Business Media New York. 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 P21 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.