Synthesis and biological evaluation of novel steroidal 5α, 8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Bu, Ming; Cao, Tingting; Li, Hongxia; Guo, Mingzhou; Yang, Burton B.; Zeng, Chengchu; Zhou, Yue; Zhang, Na; Hu, Liming
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 16(2017)
• Page Start: 3856
• Page End: 3861
• Publication Date: 2017-08-15
• Subjects: Ergosterol peroxide -- Endoperoxide -- Photooxygenation -- Steroidal derivatives -- Cytotoxic activities; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.06.048
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Inspired by the significant anti-cancer activity of our previously screened natural ergosterol peroxide (EP, 1 ), we synthesized and characterized a series of novel 5α, 8α-epidioxyandrost-3β-ol-17-( O -phenylacetamide)oxime derivatives (9a –o ). The anti-proliferative activity of the synthesized compounds against human hepatocellular carcinoma cells (HepG2, Sk-Hep1) and human breast cancer cells (MCF-7, MDA-MB231) were investigated. Compounds9d, 9f, 9h, 9j and9m displayed good anti-proliferative activity (most IC50 < 20 μM) in vitro . Furthermore, fluorescence imaging showed that the designed coumarin-9d conjugate (12 ) localized mainly in mitochondria, leading to enhanced anticancer activities over the parent structure.