Taxol, a new source of anticancer drug, is an effective and commonly used anticancer drug, but it can only be collected from the needle-like leaves of an endangered plant at present, and the demand for this drug is likely to exceed the production capacity of this tree. Recently, researchers announced at a meeting of the American Chemical Society that they had isolated this compound from hazel trees and fungi. This discovery may provide enough new sources for the drug, and may also greatly reduce its cost. Paclitaxel, also known as paclitaxel, is one of the most popular cancer drugs in the world. It is used to treat uterine cancer and breast cancer, and many breast cancer patients still take it to prevent the recurrence of cancer. Although the supply of this drug is still sufficient, the demand may increase soon: researchers are testing the efficacy of this drug for Alzheimer's disease, multiple sclerosis and other cancers. If the drug is really effective for the above diseases, then the drug will become in short supply. Because the drug is extracted from the needles of Taxus Pacific and then processed. Taxus Pacific is an endangered plant, which grows on the Pacific northwest coast of North America. Angela Hoffman, a chemist at Portland University in Oregon, USA, has been looking for ways to increase the yield of taxol in Taxus chinensis. Unexpectedly, she found a new source of the compound in another completely unrelated research topic. She and her colleagues were studying hazel trees, trying to find out why some hazel trees were more susceptible to Fusarium wilt. The disease destroyed hazel trees in Willamette Valley, Oregon. The researchers extracted extracts from several hazel trees and purified and analyzed these samples. Hoffman found the chemical characteristics of paclitaxel in it. Hoffman and her colleagues found that the leaves, branches and fruits of hazelnut contain paclitaxel, although the content is only 10% of that of Taxus chinensis. They also found that fungi growing on hazel trees can also produce paclitaxel. David Hawke said that in the end, the discovery of fungi may be the most valuable. David Hawke is a natural product expert in a pharmaceutical company in Worcester County, Massachusetts, USA. He said that yew also contains taxol-producing fungi. Hawke stressed that if the drug can be produced in vats with fungi, "it will definitely be valuable."
The medicinal value of Taxus chinensis mainly lies in its extract-secondary metabolic derivative-paclitaxel. According to the research results of Dr. Fang (Fang 1997 graduated from Peking Union Medical College and studied under Professor Liang), paclitaxel is the first anti-tumor active component isolated from the bark of Taxus brevifolia. It is one of the best drugs for the treatment of metastatic ovarian cancer and breast cancer, and also has obvious curative effect on lung cancer and esophageal cancer, and has obvious inhibitory effect on nephritis and parvovirus inflammation. The anti-cancer mechanism of paclitaxel is that paclitaxel can bind to trace proteins, promote their polymerization, inhibit the mitosis of cancer cells and effectively prevent the proliferation of cancer cells.
In order to reduce the damage to wild Taxus resources, people began to extract the precursor compound 10- deacetylbaccatin ⅲ from the branches and leaves of Taxus chinensis, and then semi-synthesized it to prepare medicinal taxol. Paclitaxel is a broad-spectrum and powerful anticancer drug recognized in the world at present, which has a unique anticancer mechanism.
The earliest report abroad was 197 1 extracting paclitaxel from Taxus chinensis in the United States, and 1992 was approved for clinical use by the US Food and Drug Administration (FDA). It has been proved to be effective for a variety of cancers, especially ovarian cancer and breast cancer, with a cure rate of 33% and an effective rate of 75%.
On the other hand, on a global scale, countries around the world gradually accept the treatment methods and principles of traditional medicine (traditional medicine refers to the medical methods to protect and restore health before the emergence of modern medicine). China has a long history in traditional medicine, such as anesthesia, acupuncture and Chinese herbal medicine.
Appraised by authoritative departments and related reports, China yew has a certain content in refined taxol. The content of Taxus cuspidata and Taxus mairei is higher, and the content of Taxus cuspidata with special growth environment is the highest (the content can reach two ten thousandths). The unique climatic conditions are favorable for the deposition of plant dry matter. If Taxus cuspidata is moved to the south properly, the growth period can be increased, the growth environment can be improved, the synthesis of effective components in plants can be facilitated, and the content and quality can be improved.
At present, paclitaxel has become the first anti-tumor drug in the world. Meanwhile, clinical trials of paclitaxel for Alzheimer's disease and other cancers are being conducted abroad.
At present, there are three ways to obtain paclitaxel: 1. Natural extraction, 2. Synthetic, 3. Semi-synthetic and 4. Biological fermentation. The latter three methods mostly stay in the laboratory stage.
(1) Taxol biosynthesis;
The molecular formula of paclitaxel is C47H5 1NO 14, which is a natural secondary metabolite with terpenoid cyclic structure. It is mainly composed of taxane ring and side chain. It is of great significance to study its biosynthesis to improve the synthesis efficiency, clone combination, form key enzyme genes and increase the yield of paclitaxel. At present, the key is whether we can find one or two key enzymes and purify and clone their genes. It remains to be seen whether the cloning of Taxus gene can be broken through, but the imaginative way people have found is still in the laboratory stage.
(2) Chemical synthesis of paclitaxel
According to research and reports, the activity of 10- deacetylbaccatin ⅲ isolated from Taxus plants is obviously lower than that of paclitaxel, but it can be extracted from Taxus needles. This substance can synthesize paclitaxel through four chemical processes. Great progress has been made in solving the new source of paclitaxel. The American research team led by Dr. NICOLAOU reported the results of total synthesis of paclitaxel by chemical methods in 1994. However, chemical synthesis has not completely broken through in essence and has no application value at present.
(2) Microbial synthesis of paclitaxel
STTERLE et al. isolated a parasitic fungus (Taxomyces andarea) from the phloem of Taxus brevifolia, which can produce taxol and related hydrocarbons in a specific culture medium, but the current yield is extremely low and cannot be used for production. Recombinant DNA technology is expected to improve the yield of paclitaxel.
Besides bark, root is the organ with the highest taxol content. People use Agrobacterium rhizogenes to soak the explants of Taxus plants to induce rooting. This method does not need exogenous hormones, the hair roots grow rapidly and the genetic traits are stable, so it is paid attention to. If we can find a way to synthesize paclitaxel or its similar derivatives, combine the key enzymes obtained by microbial synthesis with the cloning of Taxus related genes, we can make a breakthrough in this method.
With the introduction of the 5th Beijing Biomedical Development Forum, the general development process of extracting paclitaxel from plants is as follows:
Since the 1960s, the discovery of new anticancer drugs mainly comes from the metabolites of primitive plants, that is, several anticancer chemotherapy reagents currently used, which are not compounds extracted from higher plants.
Such as "Catharanthus roseus alkaloids" isolated from Catharanthus roseus.
Epipodophyllotoxin derivatives isolated from podophyllum.
Camptothecin derivatives isolated from Camptotheca acuminata
So far, the "Taxus dichotoma" component isolated from Taxus chinensis has been obtained.
Related technologies and equipment for extracting paclitaxel;
1. Key technologies and related data of extracting taxol from Taxus chinensis.
2. Precise determination methods, quality standards and related data of paclitaxel content.
3. Impurity removal and ultra-clean equipment.
4. HPLC and HPLC analytical columns, etc.
Several antitumor drugs made from paclitaxel;
1. daksu
Heilongjiang Taxus Technology Co., Ltd. produces broad-spectrum anticancer drugs for treating parvovirus inflammation such as breast cancer and ovarian cancer.
2. Taxus chinensis capsules
Produced by Chongqing Sino Company, it is a pure Chinese medicine for the treatment of advanced cancer, which is developed by adsorption extraction and dispersion preparation.
3. plante
A broad-spectrum anticancer drug for promoting tubulin polymerization and making it difficult to depolymerize. Thereby inhibiting the division of cancer cells. Has obvious curative effect on cervical cancer, breast cancer, small cell lung cancer and melanoma.
4. Squibb Company of the United States: paclitaxel intravenous injection or infusion.
5. A new compound paclitaxel preparation produced by European Squibb and Roche multinational company is used to treat refractory advanced breast cancer and semi-systemic (cancer cell) disseminated diseases, which brings good news to many advanced breast cancers.