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Published on: February 9, 2021
Synthesis and antitumor activity evaluation of coumarin Mannich base derivatives
Bing He1, Le Ding1, Hong-Zhou Tan1
1College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
Abstract:
Twenty-one new coumarin Mannich base derivatives (11a-u) were synthesized, which exhibited antiproliferation activities in HepG2 (liver cancer), A549 (lung cancer), MCF-7 (breast cancer), and HT-29 (colon cancer). Most of the target compounds showed the most potent activity against HepG2 cells compared with other cancer cells, compound 11g showed the strongest antiproliferative activity (2.10 μM) against HepG2, even superior to the positive control drug 5-FU(5.49 μM). The nitric oxide (NO) release of all compounds in HepG2 cells was determined, of which compound 11g showed high levels of NO release (10.8 μM). Notably, the solubility of compound 11g increased 13-fold compared with the lead 8. The preliminary cytotoxicity studies suggest that 11g had little effect on LO2 cells(normal liver cells, >50 μM). The effect of compound 11g on the apoptosis of HepG2 cells was also studied, and the results showed that the induction effect of compound 11g on apoptosis is a concentration-dependent manner. Our results indicate that compound 11g might be a promising lead for further studies.
Insights
Twenty-one novel coumarin Mannich bases were synthesized and tested for antiproliferation. Compound 11g demonstrated potent activity against liver cancer (HepG2) cells, showing improved solubility and low toxicity to normal liver cells.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Cancer Research
Background:
- Coumarin derivatives are recognized for their diverse biological activities.
- Mannich bases are versatile synthetic intermediates with potential therapeutic applications.
- Developing novel antiproliferative agents is crucial for cancer treatment.
Purpose of the Study:
- To synthesize and characterize new coumarin Mannich base derivatives.
- To evaluate the antiproliferative potential of these compounds against various human cancer cell lines.
- To identify lead compounds with potent anticancer activity and favorable physicochemical properties.
Main Methods:
- Synthesis of 21 coumarin Mannich base derivatives (11a-u).
- In vitro antiproliferation assays against HepG2, A549, MCF-7, and HT-29 cancer cell lines.
- Nitric oxide (NO) release assays and cytotoxicity studies on normal LO2 cells.
- Apoptosis induction studies on HepG2 cells.
Main Results:
- All synthesized compounds exhibited antiproliferation activities.
- Compound 11g showed the most potent activity against HepG2 cells (IC50 = 2.10 μM), outperforming the positive control 5-FU.
- Compound 11g demonstrated a 13-fold increase in solubility compared to the lead compound 8 and low toxicity to LO2 cells.
- Compound 11g induced apoptosis in HepG2 cells in a concentration-dependent manner and showed high NO release (10.8 μM).
Conclusions:
- Compound 11g is a promising lead candidate for the development of novel liver cancer therapeutics.
- The synthesized coumarin Mannich bases represent a valuable class of compounds for anticancer drug discovery.
- Further investigation into the mechanism of action and in vivo efficacy of compound 11g is warranted.
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