Synthesis and Antiproliferative Activity of Some Androstene Oximes and Their O‐Alkylated Derivatives

Abstract

In order to study the structure-activity relationship with respect to the cytotoxicity of steroidal oximes, several 6E-hydroximino-4-ene steroids and their O-alkylated derivatives were synthesized. The oxime ethers were solidified and purified by preparing their corresponding oxalate salts. The new derivatives as well as some previously synthesized ones were evaluated for in vitro antineoplastic activity against a panel of 60 cancer cell lines at 10 µM. The oximes and oxime ethers were found to have moderate to good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines.

Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C19H25NO3) a Molecule with Antiproliferative Activity

“…The compound was synthesized by the previously reported method and recrystallized in the form of yellow needles using methanol to obtain single crystals suitable for X-ray data collection [2].…”

“…Steroidal oximes have emerged as a new class of anticancer agents with either endocrine activity against aromatase and 5α-reductase enzymes or direct cytotoxicity on human cancer cells [1,2]. Particular attention has been made to study the effect of 6E-hydroximinoandrostene framework on the antineoplastic activity [2][3][4]. However, during the synthesis the oximes tend to form the mixture of Z and E-geometrical isomers.…”

“…The isolation and characterization of the desired E-isomer possesses greater challenge as the isomeric purity can affect the biological activity [4]. However, the present steroidal hydroximinoandrostene derivative was obtained as the pure E-isomer by recrystallization from methanol and the configuration of the title derivative was determined based on 1 H NMR studies [2]. Therefore, in this paper we have reported the crystal structure of 6E-hydroximino-androst-4-ene-3,17-dione in order to determine the isomeric orientation and other structural features.…”

Antiproliferative Properties of Newly Synthesized 19-Nortestosterone Analogs Without Substantial Androgenic Activity

“…A large body of evidence indicates the outstanding importance of these compounds and their versatile antitumor effects. A considerable antiproliferative action of several sets of innovative androstane analogs have been reported against a broad variety of cell lines, including prostate, breast, cervix, ovarium, leukemia, melanoma, colon, and gastric cancers ( Iványi et al, 2012 ; Ajdukovic et al, 2013 , 2015 ; Acharya and Bansal, 2014 ; Cui et al, 2015 ; Jakimov et al, 2015 ). 19-Nortestosterone derivatives, e.g., levonorgestrel, desogestrel, and dienogest, an important division of testosterone-derived molecules are widely utilized in hormone replacement therapy ( Campagnoli et al, 2005 ), contraception ( Minami et al, 2013 ; Royer and Jones, 2014 ), and treatment of endometriosis ( Minami et al, 2013 ; Miyashita et al, 2014 ).…”

Circular dichroism spectroscopy and DFT calculations in determining absolute configuration and E/Z isomers of conjugated oximes

“…Oximes and their derivatives play an important and diverse role in various fields of chemistry. Some of them are components of drugs exhibiting excellent pharmacological activities, among which analgesics, antitussive, antidepressant, and antiproliferative are worth mentioning. Moreover, oximes are proven to be useful synthons leading to, among others, fused heterocycles, β‐lactams, β‐amino acid derivatives, or to multifunctional compounds .…”