Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro.

Abstract

Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp2)-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure-activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates.

• Authors: Lu Jin, Meng-Ling Wang, Yao Lv, Xue-Yi Zeng, Chao Chen, Hai Ren, Heng Luo, Wei-Dong Pan
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 9 (May 06 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31064088 (Publication Type: Journal Article)

Chemical References

• Alkadienes
• Antineoplastic Agents
• Ethers
• Flavonoids
• propadiene

Topics

• Alkadienes (chemistry)
• Antineoplastic Agents (chemical synthesis, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Design
• Ethers (chemistry)
• Flavonoids (chemical synthesis, therapeutic use)
• Humans
• Molecular Structure
• Stereoisomerism
• Structure-Activity Relationship