Anticancer Agent Synthesis

Cancer, also called a malignant tumor, is caused by the disorder of cell proliferation, and has become one of the most common causes of morbidity and mortality in humans after cardiovascular disease. According to the International Agency for Research on Cancer (IARC), there were 18.1 million cancer cases in 2018 and are expected reach 29.5 million by 2040^[1]. Cancer patients can be treated with surgery, radiation, hormone therapy or some combinations of these methods. Generally, these treatments are followed by chemotherapy. Therefore, it is necessary to develop chemotherapeutic agents with preferable efficacy, lesser toxicity, and better selectivity. Click chemistry can attach small units to produce much more complicated molecules, thus, it is widely used in anticancer agents synthesis and many articles have been published in this field.

Applications

• Berberine derivative synthesis by CuAAC click reaction

At present, research on the anticancer activity of berberine has received much attention. However, berberine is poorly absorbed in the intestines, showing a low inhibitory effect on cancer cell growth. Fortunately, berberine derivatives are able to ameliorate this drawback of berberine. Jin and co-workers^[2] synthesized a series of triazole-containing berberine derivatives using the copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction (Scheme 1). The anticancer activity of these berberine derivatives against a panel of three human cancer cell lines, MCF-7 (breast), and SW-1990 (pancreatic) was screened. The results indicated that most of the berberine derivatives displayed notable anticancer activities against MCF-7 cells compared with berberine.

Scheme 1. General route for synthesis of triazolyl berberine derivatives.

• Pt based anticancer agent synthesis by CuAAC click reaction

Approximately 50% of cancer patients treated with chemotherapy receive a Pt (II)-based medicine such as cisplatin, carboplatin or oxaliplatin (Scheme 2). However, the clinical effectiveness of Pt (II)-based medicines is hampered by toxic side effects and both intrinsic and acquired resistance. Therefore, there has been a continued drive to develop novel classes of more effective and better-tolerate Pt (II) and Pt (IV) anticancer agents. Click reaction (such as CuAAC click reaction) represents a powerful and versatile tool that can be exploited to synthesize/develop novel Pt-based anticancer agents and to better understand the biological effects of Pt-based anticancer agents at a cellular level^[3].

Scheme 2. Structures of three clinically approved Pt (II)-based anticancer medicine.

What Can We Do?

Alfa Chemistry has a strong research foundation in the field of anticancer agent synthesis by click chemistry. We have ability to help you explore the various applications of click chemistry and provide you with related click chemistry reagents, technical advice and services. If you have problems, please don't hesitate to contact us.

References

1. Mashayekh, K.; Shiri, P. An overview of recent advances in the applications of click chemistry in the synthesis of bioconjugates with anticancer activities. ChemistrySelect. 2019, 4: 13459-13478.
2. Jin, X.; et al. Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC "click" chemistry as potential anticancer agents. Drug Design, Development and Therapy. 2014, 8: 1047-1059.
3. Farrer, N.J.; Griffith, D.M. Exploiting azide-alkyne click chemistry in the synthesis, tracking and targeting of platinum anticancer complexes. Current Opinion in Chemical Biology. 2020, 55: 59-68.