Caffeate compounds are oriented to create products to support cancer treatment
Assoc. Prof. Dr. Trinh Thi Thuy and the research team
Caffeates are derivatives of caffeic acid (CADs, CA), a fairly common substance in many common plants and foods such as coffee beans, tea, vegetables and fruits. CA has been shown to have many effects such as hypoglycemia, anti-inflammatory, antiviral, potential antioxidant, immunomodulatory and inhibitory of many cancer cell lines, including lung and colon cancer (in vitro and in vivo). Until now, CA derivatives have played an important role in the development of anticancer drugs.
Balanophora laxiflora Hemsley has been studied extensively in Asia, especially in China. As of 2022, over fifty substances have been found in this species. Screening results show that methyl caffeate (MC) compounds are quite high in jade and have positive cytotoxic activity. MC and its derivatives have been patented in the US for application in the treatment of dermatological and genital diseases such as dermatitis, carcinoma, and cervical cancer. MC is non-toxic, this is a promising candidate for the treatment of diseases associated with cancer, inflammation. Therefore, the project chose to study the process of obtaining caffeate derivatives from Balanophora laxiflora Hemsley and test their effects and mechanisms of action on some cancer cell lines, focusing more deeply on acute bone marrow cancer cell lines (OCI-AML3).
Balanophora laxiflora collected in Tuyen Quang
Methyl caffeate (MC) has good cytotoxic activity on experimental cancer cell lines (A549, T24, Huh-7, 8505, SNU-1, OCI-ALM3) and is immunosuppressive through inhibition of IL-2 expression on macrophage cell lines (RAW264.7). MC is one of the substances with a fairly high content in Jade (0.036%) and some other species. Moreover, this substance is easily obtained through semi-synthetic routes with fairly high performance from caffeic acid (AC). On the market, there are many pharmaceutical products containing caffeic acid and caffeate derivatives. From the above basis, the topic chose MC substance to create the preparation. In order to have a sufficient amount of composition, the process is selected by the subject and selectively extracted instead of running columns, the average efficiency is 0.036% (compared to dry materials).
The results of the project showed that the main substance in the preparation, methyl caffeate, has good activity, specifically activating opoptosis for acute bone marrow cancer (OCI-ALM3) cell lines. According to recently published literature, caffeyl hydrazide compounds have a beneficial effect on pro-inflammatory factors, which are related to the immune system. According to modern medicine, inflammatory and oncological processes are closely related. Moreover, recently Şevki Adem et al. 2020-2021, suggested that caffeic acid derivatives (CADs) effectively reduce the SARS-CoV-2 viral load, inhibit and shorten the infectious period. The immunomodulatory and cytokine antagonistic effects of caffeate derivatives are of special interest to scientists around the world and are evaluated as having high potential for research and development of applications in pharmaceuticals. Therefore, the project further investigates the immunomodulatory activity and inhibition of NO production of newly synthesized caffeates from AC as products of the project.
Test results show that the new caffeyl hydraride derivatives have good nitric oxide (NO) inhibitory activity. Notably, fluorobenzoic hydraride has the strongest inhibitory activity with IC5011.90±0.73 μM, which is twice as strong as the positive control (L-NMMA). The results of these active tests are the basis for guiding further studies. Test results show that the new caffeyl hydraride derivatives have good nitric oxide (NO) inhibitory activity. Notably, fluorobenzoic hydraride has the strongest inhibitory activity with IC5011.90±0.73 μM, which is twice as strong as the positive control (L-NMMA). The results of these activity tests are the basis for guiding further studies. The research team has developed a process to extract and extract methyl caffeate (MC) compound from Jade Crane tree (scale 2g MC / batch, average efficiency 0.036%). Caffeate-MC preparations create safety, meet food hygiene and safety standards (according to the circular of the Ministry of Health regulating raw materials for preparing health foods).
The new contribution of the project is that for the first-time MC has been reported to significantly inhibit OCI-AML3 cell proliferation and activate apoptosis cell death. The team synthesized 8 new caffeyl hydrazide derivatives. These substances have very good anti-inflammatory activity.
Synthetic caffeate compounds are good inhibitors of nitric oxide (NO) production, so the leaders and team wish to continue researching them in the direction of anti-inflammatory activity for application in pharmaceuticals.
Translated by Phuong Ha
Link to Vietnamese version