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    Home > Biochemistry News > Biotechnology News > Application of disulfur bonds in chemical drugs

    Application of disulfur bonds in chemical drugs

    • Last Update: 2020-06-02
    • Source: Internet
    • Author: User
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    Disulfur bond (S-S key) is an important chemical officer group, mainly found in various natural small molecular compounds and biological protein structuresSome small molecular compounds containing disulfur bonds show a wealth of biological activity, such as the antioxidant activity of our familiar lipoic acid and acetylcholine receptor inhibitory activity of sand silkworm toxinIn organisms, the main functions of the disulfur bond include helping protein structure to cure, controlling cell signaling and participating in metabolic pathwaysBecause disulfur bond is low lysotoxic in the body, and it can break in the external environment under the presence of the prototype glutathione (GSH), so many drug developers introduce disulfur bonds into the drug structure to achieve better therapeutic resultsin the drug database (as of July 24, 2019), as many as 113 dissulfur-key chemicals, of which 34 were on the marketBy treatment area, these drugs are mainly distributed in nutritional diseases, tumors, cardiovascular diseases, endocrine and metabolic diseases, urogenital diseases and other fields, involving mainly the targets of growth inhibitor receptor (SSTR), folic acid receptor (FOLR), fibrinogen receptor (GP IIb/IIIa), arginine vasopressin receptor (AVPR), oxytocin receptor (OXTR) and other similar to the vitaminNext, we introduce some drugs containing disulfur bonds in combination with therapeutic areas and indicationsdata collated from the drug database
    1nutritional diseases1882, Dutch doctor Eijkmann in the experiment found that brown rice rice skin contains a class of active substances to treat the then popular "foot gas disease." In 1911, the Polish chemist Finco first isolated the substance from plants and named it "foot-resistant vitammine", the first water-soluble vitamin, vitamin B1 (also known as thiamine), to be foundToday, it has been found that vitamin B1 is not only present in rice bran, it is also in dry yeast, lean meat, wheat bran and peanuts and other animal and plant foods, and its role is not limited to anti-foot gas disease, vitamin B1 has to maintain the normal function of the heart, nerve and digestive system and participate in the role of sugar metabolism has long been the consensusin the current market of drugs containing disulfur bonds, there are 6 for the treatment of nutritional diseases, their indications are all vitamin B1 deficiency, through a simple analysis of the chemical structure of these six drugs, we can not be difficult to find that they are all by the disulfur key and vitamin B1 in the body's metabolic intermediates linked to the vitamin B1 analoguesThey can be converted to bioactive thiamine pyrophosphate (TTP) in the body more quickly than vitamin B12.
    Anti-tumor drugthe second largest use of disulfur key drug is as an anti-tumor drug, at present, there are 5 disulfur key anti-tumor drugs on the market, 27 anti-tumor drugs in the development stage Of these, 4 drugs were on the market and 9 were targeted by growth inhibitor receptors (SSTR), and five were targeted by folic acid receptors (FOLR), which accounted for 56.2% of the total number of dioxin scoundrels in the field This paragraph therefore focuses on these two types of drugs growth inhibitor (SST) is an important hormone-regulating peptide for cell proliferation and differentiation, in recent years, SST and its analogues have attracted more and more attention to the inhibition effect of tumors, and the clinical application of SST to treat neuroendocrine tumors has achieved good results The new drug Lutetium (177Lu) oxodotretide, developed by Advanced Accelerator Applications, is an SSTR2 antagonist As a Lu-177-labeled growth inhibitor analogue, the drug's positive results in phase III clinical trialnettera-1 in patients with intestinal neuroendocrine tumor (NETs) were announced at the 2018 EMSO conference The data show that Lutathera therapy can significantly reduce the risk of disease progression or death by about 80% compared to the use of octreotide LAR alone, and is not affected by liver tumor burden (LTB), alkaline phosphatase (ALP) levels in the liver, or tumor diameter size folic acid, also known as vitamin M, or butterfly-lyceglutine, is mainly involved in important processes such as methionine circulation, methylation reactions and DNA synthesis in organisms Folic acid receptor is a glycophosphosphosphatidyl (GPI) conjugate protein that is overexpressed on the surface of many tumor cells and has a low level of expression on normal cells, and because folic acid receptors are highly affinity with folic acid and its derivatives, people begin to develop anti-tumor drugs at the target At present, there is no folic acid receptor target drug market, but in the clinical stage of the drug, the proportion of chemical drugs containing disulfur bonds up to 50%, has a certain development prospects 3.
    Cardiovascular disease On May 18, 1998, the second-sulfur-type drug Eptifibatide was approved by the U.S Food and Drug Administration (FDA), which is owned by Millennium Pharmaceuticals (a subsidiary of Takeda) and Merck and Merc, MSD) was jointly developed to inhibit platelet aggregation by preventing the combination of fibrinogen (GP IIb/IIIa), von Willebrand factor and other adhesionligation with GP IIb/IIIa receptors, and was approved for the treatment of patients receiving medication for acute coronary artery syndrome (ACS) or treated with coronary artery intervention (PCI) another representative of the disulfur cosin in the cardiovascular field is Arginine vasopressin, which plays an important role in osmotic pressure regulation, cardiovascular function control and maintaining internal environmental stability 4.
    Urinary diseases for a long time, preterm birth is a serious problem for obstetricians, it is the main cause of perinatal death and morbidity, the current treatment is mainly the use of anti-premature drugs to inhibit uterine contraction However, types of drugs such as beta epinephrine receptor agonists, prostaglandin synthesis inhibitors, and calcium ion channel blockers have adverse effects on both mother and fetus Therefore, a more specific anti-premature drug is clinically needed As a new anti-premature drug, oxytocin receptor antagonists have higher specificity and fewer adverse reactions than other types of drugs mentioned above Atosiban, which contains the disulfur bond, is a oxytocin analogue that fights childbirth during premature birth and is usually given in the form of acetate 5.
    Other listed drugs with disulfur bonds anti-tumor drugs: cardiovascular disease drugs: endocrine and metabolic disease drugs: digestive disorders drugs: drugs genitourinary diseases: drugs for blood system diseases: the nervous system drugs: antipsychotic drugs: eye disease drugs: severculosis and connective tissue disease drugs: references: 1 JIANG C S, etc Disulfide - and multisulfide-containing metabolites from marine organisms Chem Rev, 2011, 112 (4): 2179-2207 2 GO Y M, etc Thio Vdisulfide redox states in signaling and sensing Crit Rev Biochem Mol Biol, 2013, 48 (2): 173-181 3 Sun Lulu, Zhang Shige Vitamin B1 (thiamine) deficiency (foot gas disease) and vitamin B1 China Pharmacy, 2003, Vol 14, No 6: 383-384.
    4 Yang Shaoqi et al Experimental study on the effect of growth of human liver cancer cells by growth inhibitor receptor-specific agonists Journal of Ningxia Medical University, 2011, Volume 33, No 2: 126-128 5 Novartis presentation of new Lutathera® NETTER-1 data at ESMO demonstrateing the building in PFS of the liver leave tumor burden, Novartis, 2018/10/19 6 Alberg, A.J., etc The risk cervic al cancer in relation to serum sofe of vitamin B12, and homocysteine Cancer Epidemiol Biomarkers PrevG, 2000, 9 (7): 761-764 7 Medicines Data Website: Http://data.pharmacodia.com/web/homePage/index.
    8 Oliver G On the tha ei s of extracts of the pituitary and certain other other glander organ J Physiol, 1985, 18 (7): 27-31 9 Pompeii Study of the treatment of premature birth by oxytocin receptor blocker Atosiban Journal of Medical Graduate Science, 2003, Vol 16, No 9: 702-704.
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