Antitumor activities of biscoumarin and dihydropyran derivatives. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Zhou, Hai-Yu; Dong, Feng-Quan; Du, Xin-Liang; Zhou, Zhi-Kun; Huo, Hai-Ru; Wang, Wei-Hao; Zhan, Hong-Dan; Dai, Yi-Fei; Jing Meng, ; Sui, Yun-Peng; Li, Jing; Sui, Feng; Zhai, Yun-Hui
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 16(2016)
• Page Start: 3876
• Page End: 3880
• Publication Date: 2016-08-15
• Subjects: Biscoumarin -- Dihydropyran -- X-ray -- Antitumor -- Apoptosis -- Acute toxicity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.07.023
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Two novel series of biscoumarin (1 –4 ) and dihydropyran (5 –16 ) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for their antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds2, 7, 10 and13 confirmed the structures of these compounds. Compounds1 –4 showed the most potent antitumor activity among the total 16 derivatives. More interestingly, preliminary mechanism studies revealed that the most potent compound4 induced apoptosis and arrested the cell cycle at the S phase in HUTU80 cells. Additionally, the increased accumulation of HUTU80 cells in the sub G1 peak further pointed to the occurence of the cell apoptosis. The selectivity index analysis demonstrated that all the biscoumarin compounds (SI = 3.1–7.5) possess higher selectivity towards intestinal epithelial adenocarcinoma cell line (HuTu80) than positive control drug carboplatin (SI = 1.6–1.8). The biscoumarin compounds also showed no obvious acute toxicity on mice.