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Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti-Tumor Activity
Jiatong Li1,2, Ao Gu1,2, Meng-Yao Li1,2
1State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 200032, Shanghai, China.
Abstract:
Pancreatobililary cancers are fatal solid tumors that pose a significant threat to human life. It is imperative to investigate novel small molecule active compounds for controlling these cancers. Heterocyclic compounds (e. g. gemcitabine) and multi-substituted alkenes (e. g. resveratrol) are commonly applied in tumor treatment. Researchers have proposed that the synthesis of new trisubstituted alkenes containing heteroaromatic rings by combining these two scaffolds may be a fresh strategy to develop new active molecules. In this study, we utilized alkenyl bromide and heteroaryl boronic acid as substrates, employing Suzuki coupling to generate a series of triarylethylenes featuring nitrogen, oxygen, and sulfur atoms. Through in vitro experiments, the results indicated that some compounds exhibited remarkable anti-tumor efficacy (e. g. IC50[3be, GBC-SD]=0.13 μM and IC50[3be, PANC-1]=0.27 μM). The results further demonstrated that the antitumor efficacy of these compounds was dependent on the heteroatom, π-system, skeleton-bonding site, and substituent type.
Insights
Novel trisubstituted alkenes combining heterocyclic compounds and multi-substituted alkenes show potent anti-tumor activity against pancreatobiliary cancers. These new molecules offer a promising strategy for developing effective small molecule cancer therapeutics.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Cancer Research
Background:
- Pancreatobiliary cancers are aggressive solid tumors with limited treatment options.
- Novel small molecule therapeutics are crucial for improving patient outcomes.
- Combining heterocyclic compounds and multi-substituted alkenes presents a novel strategy for drug discovery.
Purpose of the Study:
- To synthesize and evaluate new trisubstituted alkenes containing heteroaromatic rings for anti-cancer activity.
- To explore the potential of combining heterocyclic scaffolds with alkene structures.
- To identify novel small molecules for pancreatobiliary cancer treatment.
Main Methods:
- Suzuki coupling reaction was employed to synthesize triarylethylenes.
- Alkenyl bromide and heteroaryl boronic acid were used as substrates.
- In vitro anti-tumor efficacy was assessed using cell viability assays.
Main Results:
- Several synthesized triarylethylenes demonstrated significant anti-tumor efficacy against pancreatobiliary cancer cell lines.
- Potent activity was observed with IC50 values as low as 0.13 μM (GBC-SD) and 0.27 μM (PANC-1).
- Anti-tumor efficacy was found to be dependent on heteroatom type, π-system, bonding site, and substituents.
Conclusions:
- The novel trisubstituted alkenes are promising candidates for pancreatobiliary cancer therapy.
- The study highlights the potential of hybrid molecular scaffolds in cancer drug development.
- Further investigation into structure-activity relationships can optimize therapeutic potential.
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