The Oxime Ethers with Heterocyclic, Alicyclic and Aromatic Moiety as Potential Anti-Cancer Agents

Abstract

Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence, there is an urgent need to search for new molecules that would be more effective in destroying cancer cells. In this study, 1-(benzofuran-2-yl)ethan-1-one oxime and 26 oxime ethers containing heterocyclic, alicyclic or aromatic moiety were screened for their cytotoxicity against HeLa cancer cell line. The most promising derivatives with potential antitumor activity were 2-(cyclohexylideneaminoxy)acetic acid (18) and (E)-acetophenone O-2-morpholinoethyl oxime (22), which reduced the viability of HeLa cells below 20% of control at concentrations of 100–250 μg/mL. Some oxime ethers, namely thiazole and benzothiophene derivatives (24–27), also reduced HeLa cell viability at similar concentrations but with lower efficiency. Further cytotoxicity evaluation confirmed the specific toxicity of (E)-acetophenone O-2-morpholinoethyl oxime (22) against A-549, Caco-2, and HeLa cancer cells, with an EC50 around 7 μg/mL (30 μM). The most potent and specific compound was (E)-1-(benzothiophene-2-yl)ethanone O-4-methoxybenzyl oxime (27), which was selective for Caco-2 (with EC50 116 μg/mL) and HeLa (with EC50 28 μg/mL) cells. Considering the bioavailability parameters, the tested derivatives meet the criteria for good absorption and permeation. The presented results allow us to conclude that oxime ethers deserve more scientific attention and further research on their chemotherapeutic activity.

Oxime chemistry in crop protection

“…Also, several insecticidally active aldoximes are known. The NADH-coenzyme Q reductase (Complex I) inhibiting pyrazole derivative fenpyroximate (7) is used as contact acaricide against Panonychus ulmi (European red mite) and Tetranychus urticae (two-spotted spider mite) mainly in fruit, citrus and cotton. It not only leads to a rapid knockdown of mobile stages, but also suppresses the molting process of larvae.…”

“…Several million tons of cyclohexanone are converted each year into its free oxime during the industrial manufacturing of caprolactam, the Nylon-6 precursor. 6 Oximes are also used as pharmaceuticals (e.g., fluvoxamine and oxiconazole), 7 perfume fragrances (e.g., Buccoxime® and Stemone®), 8 artificial sweeteners (e.g., perillartine) 9 and antidotes for nerve agent poisonings (e.g., pralidoxime and obidoxime). 10 In addition, oximes are commonly used as ligands and sequestering agents for metal ions and chelators in metallurgy.…”

A Review of Biologically Active Oxime Ethers

“…EC 50 for this compound ( 93 ) was 0.075 μM, indicating that they have significant estrogen responsive element (ERE) mediated transcriptional activity [ 95 ]. Kosmalski et al [ 96 ] screened the oxime ethers with heterocyclic, alicyclic and aromatic moieties for their cytotoxicity. The most potent and specific compound was ( E )-1-(benzothiophene-2-yl)ethanone O -4-methoxybenzyl oxime ( 94 ), which was selective for HeLa (with EC 50 = 27.9 μg/mL) cells.…”