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Name: 2-mercaptopropionylglycine
Generic Names: Alpha-mercaptopropionylglycine[1]; Acadione; Capen; Epatiol; N-(2-Mercaptopropionyl)glycine; Thiosol; MPG; Thiola; Thiopronine[2]; N-(2-Mercapto-1-oxopropyl)glycine; Captimer; Meprin; Mercaptopropionylglycine; Sutilan; Thiolpropionamidoacetic acid; Tioglis; Thiopronin; Vincol[3]; Mucolysin[4]; Tiopronin[5];
IUPAC name: 2-(2-sulfanylpropanoylamino)acetic acid [2]
Molecular Formula: C5H9NO3S [7],[6]
Molecular Weight: 163.1949 [g/mol] [6]
Structure: [8],[13]
Functional Group/chemical constitution:: Free SH group[9], free carboxyl group[10]
Chemical Nature: It is a condensation product due to the peptide linkage between thiolactic acid and glycine. It has high redox potential and belongs to the class with the highest reductive potency among all known -SH compounds[11].
Tiopronin is a white crystalline powder which is freely soluble in water[7].
Compared with the SH group of isothiourea type compounds, the free SH group of Meprin seems extremely stable [12]. Neutralization of the free carboxyl group enhances the SH activity: pK' SH= 8.47.The highest SH activity was found between pH 6 and 9; below pH 5 and over pH 9, respectively there was a considerably lower activity. Heavy metal ions (Ag+, Hg2+) react easily with the SH group of Meprin[9].
It is negatively charged at physiological pH[13].
Neutralization of the carboxyl group decreases the stability of the sulfhydryl groups [12].
Tiopronin possesses stronger antioxidant activity in weak acid and neutral solutions than in the weak alkaline solution [14].
Before injecting the drug in animal, MPG is dissolved in distilled water and usually the pH is adjusted to 6.4 with 0.1N NaOH, as the aqueous solution of drug is highly acidic[15],[16], [17]
Active Ingradients:
Inactive Ingredients THIOLA tablets: Calcium carbonate, carnauba wax, ethyl cellulose, Eudragit E 100, hydroxy-propyl cellulose, lactose, magnesium stearate, povidone, sugar, talc, titanium dioxide[7]
Source: -
Actions & Indications: Pharmcological Action-
Anti-allergic[18] ,
Used as Detoxifier in Japan[20],
Metal Thiochelator[21], [22],
Thiol Radioprotector [23],
Free radical scavenger[24],
Therapeutic benefits/Indications-
Hepatoprotective- it reversed the effect of a carcinogen on liver enzymes[25],[26], [27],[29] and anti-cataract agent[28], offers cardioprotection in ischemic-reperfused heart[30], [31], also inhibits complement-mediated myocardial injury[32].
2-MPG is used in therapy of heavy metal poisoning, chronic hepatitis and hemochromatosis[33].
It is also used in treatment of rheumatoid arthritis in France[34].
It is recommended in treatment of cystinuria; although adverse effects like Nephrotic syndrome have been recorded in some cases[35], [36].
Tiopronin has been used clinically in the treatment of several disorders [37],[38], [39].
preclinical data(benefits):
Tiopronin also has good therapeutic effects against the liver damage due to viral hepatitis, drug hepatitis, alcohol hepatitis [40], anti-tuberculosis drugs[41].
Good therapeutic effect of Tiopronin on the clearance of oxygen free radicals in chronic hepatitis B patients [42] and hence thought to be of value in treatment of chronic hepatitis [43], also has been employed in a study for the management of acute viral hepatitis[44] as well as chronic viral hepatitis[45].
MPG has been used to modify radiation damage to human tissues[46]and radiotherapy patients [47]such as for suppressing liver damage in patients after radiotherapy[40], suppressing the occurrence of late injury after radiotherapy for cervical cancer[49], for reduction of the radiation-induced chromosome aberrations in lymphocytes in patients undergoing pelvic radiation(250mg i.v.).MPG (250 mg i.v.) protects against radiation-induced leucopenia in man[47].
Tiopronin prevented leukopenia[48], hepatotoxicity[40], [49], hepatotoxicity in breast cancer[50] after chemotherapy, also reduced neutropenia when given concurrent with first-line chemotherapy and improved 1-year overall survival in patients with metastatic non-small-cell lung cancer [51]. Tiopronin is found to be effective for prevention and treatment on side effects in patients with hepatocellular carcinoma after interventional therapy [52].
Tiopronin is shown to increase the sensitivity of multiple drug resistant human cancer cells lines to certain chemotherapeutic drugs like etoposide, adriamycin[53],[54].
Also it is found to be a putative neuroprotective agent, in aneurysmal subarachnoid hemorrhage, in phase I clinical trial [55].
Therapeutic usefulness of the drug in clinical conditions with defective neutrophil function is suggested [56].
Tiopronin reverses the ROM (Reactive Oxygen Metabolites) induced inhibition of NK cell-mediated killing of K562 cell in a certain extent [57].
It is shown to inhibit platelet aggregation in reversible manner[58] and hence used in a study for human platelet storage[59].
After a treatment with tiopronin, an improvement in phagocytosis process in Pulmonary alveolar macrophages (PAM) and in number of lymphocytes is found in patients suffering from obstructive chronic bronchopneumonia [60].
MPG at pharmaceutical doses exerts antiproliferating effects on human breast cancer cells[61].
Tiopronin enhances migration of polymorphonuclear leukocytes (PMNs). The enhancing effect consists partly of a chemokinetic, and partly of a chemotactic effect[62].
Tiopronin is also reported to be employed as protecting ligand for bimetal nanoparticles like AgAu MPC(Monolayer protected clusters) [63].
In animals-
Generally found to be effective against disorders that are linked to abnormal free radical production [64], [5], [30], [33].
The preventive and therapeutic effects of (±)-tiopronin and (-)-tiopronin on leucopenia induced by radiation were found [65]. MPG also prevented leukopenia induced by radiotherapy in mice[66].
2-MPG is shown to prevent the synthesis of radiation-induced abnormalities in animals [46], [67], [68]. Reduces myocardial infract size in dogs[69]; but not in rabbits[70], protect against high fat diet induced steatohepatitis in rats [71], against acute pancreatitis in rats[72].
N-(2-mercaptopropionyl)-glycine was able to reduce Cigarette Smoke-induced alveolar enlargement, neutrophil influx into alveoli, redox imbalance and lung functional impairment in mice [73].
MPG was shown to be ineffective in reducing radiation induced GI death, but delayed the onset of the syndrome in Swiss albino mice exposed to whole-body gamma irradiation[74].
It is shown to protect rats and dogs liver during ischemia/reperfusion process[75].
It could offer cardioprotection in canine model[76].
therapeutic effect of tiopronin on hepatolenticular degeneration (HLD) in rats is observed [77], [78].
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