88495-63-0 Usage
Antiparasitic drug
Artesunate is a kind of commonly used anti-parasitic drug and belongs to reduced artemisinin succinate monoester, and is the derivative of artemisinin containing a sesquiterpene lactone structure, and has a stronger efficacy on treating parasite than artemisinin and is also effective on treating chloroquine resistant strains. It acts on the Plasmodium schizonts on the erythrocytic stage. It takes effect by inhibiting cytochrome oxidase through reduced artemisinin to achievement of the inhibition on the function of cytochrome oxidase of malaria parasite surface membrane-food vacuole membrane, mitochondrial membrane, and thus blocking the supplying of nutrition from the host cell cytoplasm. It has a strong killing effect on the asexual form of plasmodium with a rapid efficacy enabling the rapid control of the onset of malaria. It has good efficacy on treating cerebral malaria, falciparum malaria and vivax malaria with similar efficacy in treating chloroquine-resistant strain of the falciparum malaria, especially with more significant effect on treating cerebral malaria. It can quickly control the emergence of malaria but has no effect on falciparum malaria gametophyte. It has a shorter T1/2 than artemether with blood concentration rapid decreasing after intravenous injection. Its T1/2 is about 30 min. It is widely distributed in the body with the content in intestine, liver, kidney being relative high. Urine and fecal excretion account for only a small fraction. It mainly undergoes metabolic conversion. It is clinically suitable for rescue of critically ill patients with acute malaria and can be used as the first-choice drug for the treatment of patients with cerebral malaria and a variety of dangerous malaria. But its shortcoming is the recrudescence rate. No adverse reactions have been observed at the recommended therapeutic dose; the application of large doses may cause a transient reduction of the outer peripheral reticulocyte which will return to normal level after stopping drug. Women within 2 months of pregnancy should be disabled. Whether it will cause teratogenicity demands further study.
Dosage and administration
Powder: 60mg; each artesunate is also attached with one 5% sodium bicarbonate injection. Upon application, first dissolve the drug in sodium bicarbonate injection, and then diluted to 10 ml with glucose injection after intravenous infusion at a rate of 3~4ml/min. For the treatment of patients of chloroquine-resistant falciparum malaria: 60 mg per time with the first dose being doubled; intravenously inject 1 times per day with 4 days as a course of treatment. The total dose is 300mg. When the symptom gets controlled, you can change with other anti-malarial drugs to reduce the recrudescence rate. The exact dosage and tablets should be according to the exact condition.
The above information is edited by the lookchem of Dai Xiongfeng.
Clinical application
The clinical application of artesunate has been as long as ten years. It is made through using the artemisia annua grass which is unique in China as raw material for extracting the active ingredient artemisinin and further going through chemical synthesis. Its major role is in treating plasmodia asexual form. It is also currently the only artemisinin derivatives which can be made into water-soluble formulation. It can be used to kill the parasite in inner phase of red blood cells to achieve the anti-malarial effect, and therefore being used in patients with various types of malaria, especially for treating and saving the patients with anti-chloroquine and anti-piperaquine falciparum malaria and severe-type cerebral malaria. It is characterized by high anti-malarial activity, high rate of fever abatement, short parasite clearance time and low drug toxic and side effects. It is the first-choice of drugs for the treatment of severe malaria.
For the application of artesunate tablets, using a total amount of 0.28 g in 3d course of treatment and a total amount of 0.44 g in 5d course of treatment, wherein applying the total amount 0.44 g (equivalent to 8.8 mg/kg) in 5d course for treatment of falciparum malaria can lead to the protozoa recrudescence rate being as low as 4.4% after clinical curing of the patients with no significant toxicity and side effect and no decline in reticulocytes, clarifying that the patients have good tolerance on this dose. Oral administration has low toxicity and rapid efficacy and is more convenient and simple for applying.
Applying 0.24 g/kg of artesunate for treatment of 72 cases of chloroquine-resistant falciparum malaria results in both the cooling time and asexual parasite clearance time being within 36 h and severely sicken patients being clinically cured. This clarifies that artesunate injection has many advantages including rapid insecticidal effect, short-term efficacy, safety, etc., it is suitable for the treatment and saving of patients with severe chloroquine-resistant falciparum malaria.
Uses
Different sources of media describe the Uses of 88495-63-0 differently. You can refer to the following data:
1. Artesunate is a kind of anti-malarial drug that has a relative strong killing effect on the asexual body of plasmodium falciparum and can result in rapid control of malaria episodes.Artesunate is dispensed as a powder of artesunic acid. This is dissolved in sodium bicarbonate (5%) to form sodium artesunate. The solution is then diluted in approximately 5 ml of 5% dextrose and given by intravenous injection or by intramuscular injection to the anterior thigh. The solution should be prepared freshly for each administration and should not be stored.
2. Artesunate, a semi-synthetic artemisinin derivative, has been shown to be effective against parasites, such as liver flukes, and has also shown cytotoxic effects on different types of tumor cell lines. artesunate belong to Antimalarial which is clinically useful for treatment of malaria and other parasitic diseases.
Chemical Properties
Fine-White Crystalline Powder. soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide, which should be purged with an inert gas. The solubility of artesunate in these solvents is approximately 20, 14, and 11 mg/ml, respectively. Artesunate is sparingly soluble in aqueous buffers.
Definition
ChEBI: Artesunate is an artemisinin derivative that is the hemisuccinate ester of the lactol resulting from the reduction of the lactone carbonyl group of artemisinin. It is used, generally as the sodium salt, for the treatment of malaria. It has a role as an antimalarial, a ferroptosis inducer and an antineoplastic agent. It is an artemisinin derivative, a sesquiterpenoid, a dicarboxylic acid monoester, a cyclic acetal, a semisynthetic derivative and a hemisuccinate.
Preparation
Artemisinin was discovered in the 1970s as a result of an extensive screening of Chinese herbal extracts in the search of new antimalarial agents. Currently, the primary method for the production of artemisinin is the isolation from dried leaves of the plant Artemisia annua. Furthermore, the global supply of this life-saving drug exclusively from natural sources remains highly limited. As a result, a novel approaches for large-scale production of artemisinin have been developed. Artesunate is prepared from dihydroartemisinin (DHA) by reacting it with succinic acid anhydride in a basic medium.A simplified and scalable synthesis of artesunate
General Description
Artesunate is a semisynthetic derivative of artemisinin used to treat malaria. It has also been shown to effective against other parasites such as liver flukes. Artesunate also demonstrates cytotoxic action against cancer cell lines of different tumor types.
Biochem/physiol Actions
Artesunate acts on the electron transport chain, generates local reactive oxygen species, and causes the depolarization of the mitochondrial membrane. It inhibits TNFα-induced production of proinflammatory cytokines via inhibition of NF-κB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes.
Mode of action
Artesunate is a water-soluble, semi-synthetic derivative of the sesquiterpine lactone artemisinin with anti-malarial, anti-schistosomiasis, antiviral, and potential anti-neoplastic activities. It acts on the electron transport chain to generate local reactive oxygen species and cause depolarization of the mitochondrial membrane. It inhibits TNF-induced proinflammatory cytokine production by inhibiting NF-κB and PI3 kinase/Akt signaling pathways in human rheumatoid arthritis fibroblast-like synoviocytes. Artesunate has also been shown to stimulate cell differentiation, arrest the cell cycle in the G1 and G2/M phases, inhibit cell proliferation, and induce apoptosis through mitochondrial and caspase signaling pathways. Artemisinin is isolated from the plant Artemisia annua.
Check Digit Verification of cas no
The CAS Registry Mumber 88495-63-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,8,4,9 and 5 respectively; the second part has 2 digits, 6 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 88495-63:
(7*8)+(6*8)+(5*4)+(4*9)+(3*5)+(2*6)+(1*3)=190
190 % 10 = 0
So 88495-63-0 is a valid CAS Registry Number.
InChI:InChI=1/C19H28O8/c1-10-4-5-13-11(2)15(16(22)23-9-7-14(20)21)24-17-19(13)12(10)6-8-18(3,25-17)26-27-19/h10-13,15,17H,4-9H2,1-3H3,(H,20,21)/t10-,11-,12+,13+,15-,17-,18-,19?/m1/s1
88495-63-0Relevant articles and documents
Synthesis, Evaluation of Anti-Toxoplasma gondii Activity in vitro and Molecular Docking of Dihydroartemisinin Derivatives
Chen, Zheng-Ai,Deng, Hao,Quan, Yin-Sheng,Quan, Zhe-Shan,Shen, Qing-Kun
, (2022/01/11)
In this work, 21 dihydroartemisinin derivatives were synthesized, their chemical structures were characterized by 1H NMR, 13H NMR and high-resolution MS techniques, and anti-Toxoplasma gondii activity in vitro was evaluated using thiazole blue (MTT) assay. The selectivity index of compound (3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trime-thyldeca-hydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl 4-oxo-4-(pyridin-4-ylamino)butanoate (E2) was 2.24, which showed the strongest anti-T. gondii activity. In addition, the results of molecular docking studies show that E2 can be a better inhibitor of T. gondii calcium-dependent protein kinase 1 (TgCDPK1). Therefore, compound E2 has good potential as a drug for T. gondii treatment, and further research is needed to clarify its mechanism of action.
Design and synthesis of novel artemisinin derivatives with potent activities against colorectal cancer in vitro and in vivo
Wang, Liang-Liang,Kong, Lingmei,Liu, Hui,Zhang, Yunqin,Zhang, Li,Liu, Xingyong,Yuan, Feng,Li, Yan,Zuo, Zhili
supporting information, (2019/09/07)
A series of novel derivatives of artemisinin-4-(arylamino)quinazoline have been designed and synthesized, and most of them showing potent in vitro cytotoxic activity against HCT116 and WM-266-4 cell lines. Compound 32 was the most active derivative against HCT116 cell line with an IC50 of 110 nM, and significantly improved the antitumor activity of the parent compounds dihydroartemisinin (DHA) (IC50 = 2.85 μM) and Gefitinib (IC50 = 19.82 μM). In vivo HCT116 xenografts assay showed that compound 32 exhibited potent antitumor activity with obvious tumor growth delay and tumor shrunken after 18 days treatment on xenografted mice, and especially without loss of body weight. Our results indicate that compounds 32 may represent a safe, novel structural lead for developing new chemotherapy of colorectal cancer.
Identification of H2S/NO-donating artemisinin derivatives as potential antileukemic agents
Chen, Xuemei,Huang, Pei,Wang, Jing,Tian, Runmei,Chen, Yan,Chen, Yongzheng,Zhang, Lei,Ma, Zhigui
, p. 501 - 511 (2020/01/13)
Three H2S/NO-donating artemisinin derivatives were designed and synthesized. Their antiproliferative activities were evaluated against human acute myeloid leukemia (AML) cell lines of K562 and K562/ADR and human normal liver cells of LO2. Biological evaluation indicated that NO-donating compound 10c exhibited the most potent cytotoxicity against leukemia cells, similar to the bioactivity of clinical drug of homoharringtonine, but showed less toxicity than homoharringtonine against LO2 cells. Further mechanism studies revealed that 10c could enhance the levels of intracellular NO and ROS, induce apoptosis and S phase cell cycle arrest, and disturb the mitochondrial membrane potential in K562 and K562/ADR cells. Western blot results demonstrated that 10c noticeably promoted autophagy by up-regulating the levels of Beclin1 and L3-II expression, inhibited the AKT signaling, and stimulated the AMPK and JNK signaling in both leukemia cell lines. Overall, 10c exhibited the potential to be a promising candidate for the therapy of AML.
