Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity
- Bioorg Med Chem Lett. 2016 Aug 1;26(15):3464-7. doi: 10.1016/j.bmcl.2016.06.043.
- 1. School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
- 2. Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
- 3. School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
- 4. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
- 5. School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: [email protected].
- 6. School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: [email protected].
- 7. School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: [email protected].
The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10μM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of Flavones to improve their tumor cell growth inhibitory activities.