Synthesis, Structural Analysis and Cytotoxic Activity of Novel A- and B-Modified d-Homo Lactone Androstane Derivative

• Published in: Journal of chemical crystallography Vol. 46; no. 2; pp. 84 - 92
• Main Authors: Savić, Marina P., Klisurić, Olivera R., Penov Gaši, Katarina M., Jakimov, Dimitar S., Sakač, Marija N., Djurendić, Evgenija A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2016
• Subjects: Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Inorganic Chemistry; Organometallic Chemistry; Original Paper; Physical Chemistry; X-ray structural analysis; Synthesis; homo lactones; In vitro cytotoxicity; Androstane derivatives
• ISSN: 1074-1542; 1572-8854
• DOI: 10.1007/s10870-016-0631-5

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.