Artesunate

INTRODUCTION

Artesunate, the active principle of the Chinese herb Artemisia annua, is a semi-synthetic derivative of artemenism (ART). Artemisia annua is a prescription medication derived from the plant Artemisia annua. .Artesunate was created in response to the need for a more hydrophilic derivative of artemisinin. ART shows remarkable activity against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. Artesunate and other artemisinin derivatives are used to treat a wide range of infectious and non-infectious diseases. Artesunate is a semi-synthetic water-soluble derivative of the sesquiterpene lactone artemisinin with antimalarial, anti-schistosomiasis, antiviral, and potential antineoplastic properties. Carbon-centred radicals form, which has been shown to damage and kills parasitic organism cell differentiation, arrests the cell cycle in the G1 and G2/M phases, inhibit cell proliferation and induce apoptosis is controlled by aresenuate gives it anticancer properties. ART was most active against leukaemia and colon cancer cell lines1(Efferth et al., 2001). Conventional cancer treatments typically include either mono-chemotherapy or a combination of radiotherapy and mono-chemotherapy. The adverse side effects of these approaches, on the other hand, have been widely reported, prompting the search for new therapeutic drugs. In this context, the scientific community began to search for novel sources of anticancer compounds in natural sources, such as traditional medicines.

Artemisinin is a compound found in the plant. It’s the basis for the malaria drug artesunate, which doctors now prescribe. Some researchers believe that artemisinin could be used instead of more aggressive cancer treatments. While most chemotherapy drugs cause cancer cells to become resistant, artemisinin does not appear to do so. Artemisinin is also non-toxic, unlike many cancer treatments. It’s also inexpensive and simple to distribute.

Description

Injection Artesunate Artesunate, a semi-synthetic artemisinin derivative, is contained in 110 mg and is intended for intravenous administration. Artesunate is an antimalarial medication. The structural formula is as follows:

Artesunate has a molecular weight of 384.43 and is a white or nearly white powder. Butanedioic acid, mono[isobutanedioic acid] is the chemical name (3R,5aS,6R,8aS,9R,10S,12R,12aR) -decahydro-3,6,9-trimethyl-3,12-epoxy-12Hpyrano[4,3-j] ester of -1,2-benzodioxepin-10-yl.C19H28O8. is the empirical formula.2(Artesunate (Artesunate): Uses, Dosage, Side Effects, Interactions, Warning, n.d.)

Artesunate for Injection is available as a white or nearly white sterile powder for Injection.  20 mL glass single-dose contains 110 mg of artesunate for the constitution in conjunction with 11 mL of the supplied sterile diluent. The constituted solution should be colourless.

Sources

.t is an annual plant that is native to China. Many countries around the world cultivate it. Its elevation in natural conditions range from 30 to 100 cm, but cultivated conditions run from 30 to 100 cm, can reach up to 200 cm and takes approximately eight months to reach full size. An intensive plant with a brownish stem and specific leaves divided into two or three leaflets. Artemisinin is primarily extracted from the leaves. Plants are typically harvested at the start of flowering when the artemisinin content in the leaves is highest. The artemisinin content is shallow, ranging from 0.01 to 0.5%.1.4 per cent of plant dry weight. Because of its poor solubility in water, artemisinin is extracted using solvents, most commonly hexane, after being harvested and dried. However, various methods of artemisinin extraction with varying artemisinin content depend on the solvent used for extraction, artemisinin. Decoction, liquid solvent extraction, pressurized solvent extraction, microwave-assisted extraction, and supercritical fluid extraction are the most common today. The primary method of industrial artemisinin extraction involves using traditional heated organic solvents such as petroleum ether and hexane. To achieve a good result, the balance between price and amount of artemisinin extracted, increased pressure, reactant temperature, or extended. In modern technologies, extraction periods are used. For removing other phytological compounds from extracted material, the crystallization process is required for purification.

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Metabolism

Plasma esterases rapidly metabolize artesunate to dihydroartemisinin (DHA). UGT1A9 and UGT2B7 glucuronidate DHA to form DHA-glucuronide. 2,8 DHA-glucuronide can go through a minor metabolic pathway to form a Furano acetate derivative. 2 CYP2A6 may play a minor role in artesunate metabolism.

The following sequence shows the metabolism diagrammatically

Artesunate is an artemisinin derivative, metabolized to DHA, which produces free radicals that inhibit the normal function of Plasmodium parasites.  It has a short duration of action due to its short half-life and moderate therapeutic index. 7,8 Patients should be counselled about the risk of post-treatment hemolytic anaemia and hypersensitivity.

Artesunate and Cancer

Iron is required for cancer cells to spread. When arteminism and iron enter a cancer cell together, they combine to form free radicals, which kill cancer cells while leaving normal cells alone. Artemisinin has been shown in studies to slow the spread of tumours. It may also cause cancer cells to do the following:

Self-destruct, Put an end to dividing and spreading and will be cut off from their blood supply. Only a few clinical trials were conducted that looked into the role of artemisinin in cancer treatment. Artemisinin has been studied in conjunction with standard cancer care, not as an alternative. More research is needed to determine whether it is functional. So far, small studies have some experts optimistic about its potential role as a treatment for various cancers, including colorectal cancer and prostate cancer.

A study was conducted in which 20 people who have colon cancer, nine were given artesunate, and the others were not. Those who received artesunate had 13% more cancer cells die than those who did not.

Melanoma.: When combined with a second drug, artesunate showed promise for people with advanced melanoma of the eye. One person was still alive 47 months after being diagnosed with this type of skin cancer. In comparison, the average survival time for this type of cancer is 2-5 months.

Cancer of the lungs: The study included 120 cases of advanced non-small-cell lung cancer. People who received a combination of artesunate and chemotherapy saw their cancer progress more slowly as compared to those who did not receive this medication

Doctors gave a form of artemisinin to ten women for 28 days to treat advanced cervical cancer. All ten went into remission, with symptoms such as pain and vaginal discharge disappearing4(Artemisinin: Could It Be a Cancer Treatment?, n.d.)

Artemisinin in Combination with Other Anticancer Drug

Combination chemotherapy is nowadays the standard of care aiming at maximizing efficacy and minimizing systemic toxicity at the same time. Multiple mechanisms of action of ARTs, which differ from traditional chemotherapeutics, propose the possibility of effective synergism of these two. It has been reported that adding artemisinin to resistant cancer cell lines causes them to become sensitive. And its derivatives to the conventional treatment (chemosensitization). Artesunate showed the ability to sensitize breast cancer cells to epirubicin in an autophagy cascade-dependent manner. In contrast, artesunate did not significantly increase the cytotoxicity of docetaxel, another commonly used anticancer drug in breast cancer. Combining dihydroartemisinin and traditional chemotherapeutics to treat lung carcinomas, cyclophosphamide, and cisplatin was shown in a murine Lewis lung carcinoma and the human non-small cell lung cancer models in mice. Both combinations of high dose dihydroartemisinin and cyclophosphamide and dihydroartemisinin and cisplatin-induced significantly reduced tumour volume compared with either therapy alone. Moreover, the incidence of spontaneous pulmonary metastasis was wholly inhibited by the combination of dihydroartemisinin with cyclophosphamide. These lines of evidence suggest that ARTs, mainly dihydroartemisinin and artesunate, possess the chemosensitizing effects and propose their future use in the fight with chemoresistant carcinomas.

Clinical trials

To date, there is a significant number of in vitro and in vivo studies describing the anticancer effects of ARTs with encouraging results. Also, several case reports documenting the reducing impact of ARTs on tumour size and growth were published. However, only a impact few clinical trials with oncological patients were completed and their results published. The most studied are patients with solid tumours: colorectal carcinoma, breast cancer, hepatocellular carcinoma and lung cancer.

Side effects

Among the possible side effects are:

Rashes on the skin

Hearing impairment

Hearing ringing

Dizziness

 Precautions

Blood problems (e.g., hemolytic anaemia) may occur due to your treatment with this medicine. The symptoms including are chills, back pain, dark urine leg, or stomach pains, bleeding gums, loss of appetite, difficulty breathing, nosebleeds fever, general body swelling, headache, pale skin, yellow skin, nausea or vomiting, sore throat, unusual tiredness or weakness, or yellow skinn, 

Other medications should not be taken unless they have been discussed with your doctor. This includes prescription and nonprescription (over-the-counter [OTC]) medications, as well as herbal and vitamin supplements.

Conclusion:

ARTs are a practical antimalarial drug class with an excellent safety profile. Multiple preclinical and clinical studies have confirmed their anticancer properties. ARTsInhibiting, the growth of solid tumours effectively reduces their size. Angiogenesis, apoptosis, and ferroptosis are induced by cell cycle arrest and the production of reactive oxygen species. As new, cutting-edge research technologies emerge, more detailed information about the various mechanisms of action of ARTs becomes available. The number of clinical trials is growing, and the results are promising. Adjuvant or neoadjuvant ARTs may become viable in treating solid tumours, specifically breast, pancreas,oeophagus, colorectal cancer, lung cancer, and other cancers. The chemosensitizing effect of artesunate and dihydroartemisinin suggests using ARTs as add-on therapy combined with conventional chemotherapeutics and will be studied in future clinical trials. ARTs may represent one of many examples of power hidden in natural sources. Following many years of research, new promising anticancer drugs may be developed and introduced to clinical use shortly.. . In summary, artemisinins have an excellent safety and tolerability profile, having been used to treat tens of millions of adults and children globally.