Design, synthesis and anticancer activities of novel otobain derivatives. Issue 1 (23rd November 2015)

• Record Type: Journal Article
• Authors: Li, Zhongzhou; Su, Hui; Yu, Weiwei; Li, Xinjun; Cheng, Hao; Liu, Mingyao; Pang, Xiufeng; Zou, Xinzhuo
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 1(2016)
• Page Start: 277
• Page End: 287
• Publication Date: 2015-11-23
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob02176f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Twenty novel racemic otobain derivatives have been designed and synthesized, among which compound27g exhibited the most potent anticancer activity. Abstract : A series of novel racemic otobain derivatives was designed and synthesised using 2-piperonyl-1, 3-dithianes in the conjugate addition–alkylation to 5 H -furan-2-one, followed by cationic cyclisation. All the synthesised compounds were consequently evaluated for their anticancer activity against several human cancers in vitro . The efficacy of the most active compound27g was comparable with etoposide, with IC50 values ranging from 1.06 μM to 4.16 μM in different cancer cell lines. Notably, compound27g strongly induced cell cycle arrest and increased the expression of mitosis-specific markers MPM-2 and phosphorylated histone H3, but it did not trigger cell apoptosis. Further a colony formation assay showed that compound27g effectively inhibited the anchor growth of lung cancer cells in a dose-dependent manner. More importantly, compound27g at 40 mg kg −1 significantly suppressed tumour volume ( P < 0.01) and tumour weight ( P < 0.05) in a human lung cancer cell xenograft mouse model without causing systematic toxicity in mice. Our findings indicated that compound27g has significant potential for further drug development.