| Identification | Back Directory | [Name]
Suramin sodium | [CAS]
129-46-4 | [Synonyms]
309f
nf060
F-309
bay205
Naganol
SURAMIN
moranyl
naganin
naganine
antrypol
bayer205
germanin
Suppressor
fourneau309
reasodiumsalt
sodiumsuramin
suraminesodium
SURAMIN SODIUM
naphuridesodium
SURAMIN SODIUM SALT
SURAMINE SODIUM SALT
SURAMIN SODIUM, 98+%
SURAMIN HEXASODIUM SALT
Suramin hexasodium salt,98%
SuraMin hexasodiuM salt, 98% 50MG
1-(3-benzamido-4-methylbenzamido)naphthalene-4,6,8-trisulfonicacidsym-3’’-u
1,3,5-naphthylenetrisulfonicacid,8,8’-(ureylenebis(m-phenylenecarbonylimino(4
8,8'-[Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bis-1,3,5-naphthalenetrisulfoni
8,8'-carbonylbisimino-3,1-phenylenecarbonylimino-(4-methyl-3,1-phenylene)carbonyliminobis-1,3,5-naphthalenetrisulfonic acid hexasodium
8,8'-CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]BIS-1,3,5-NAPHTHALENETRISULFONIC ACID HEXASODIUM
1,3,5-NAPHTHYLENETRISULFONIC ACID, 8,8'-[UREYLENEBIS[M-PHENYLENE-CARBONYLIMINO(4-METHYL-M-PHENYLENE)-CARBONYLIMINO]] DI- HEXASODIUM SALT
8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFONIC ACID HEXASODIUM SALT
1,3,5-Naphthalenetrisulfonicacid,8,8'-[carbonylbis[iMino-3,1-phenylenecarbonyliMino(4-Methyl-3,1-phenylene)carbonyliMino]]bis-,sodiuM salt (1:6)
8-[[4-Methyl-3-[[3-[[3-[[2-methyl-5-[(4,6,8-trisulfonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonic acid | [EINECS(EC#)]
204-949-3 | [Molecular Formula]
C51H34N6Na6O23S6 | [MDL Number]
MFCD00210217 | [MOL File]
129-46-4.mol | [Molecular Weight]
1429.17 |
| Chemical Properties | Back Directory | [Appearance]
White crystalline powder | [Melting point ]
>260°C (dec.) | [storage temp. ]
0-6°C | [solubility ]
H2O: >10mg/mL
| [form ]
Crystalline Powder | [color ]
White | [PH]
pH(10g/l, 25℃) : 5.0～8.0 | [Water Solubility ]
soluble | [BRN ]
3694087 | [Stability:]
Hygroscopic |
| Hazard Information | Back Directory | [Chemical Properties]
White crystalline powder | [Uses]
antiviral | [Uses]
Sodium salt of Suramin, a hepatitis C virus NS3 helicase inhibitor. Also used in the treatment of arthritis due to problematic collagen. | [Biological Activity]
Non-selective P2 purinergic antagonist. Also blocks calmodulin binding to recognition sites and G protein coupling to G protein-coupled receptors. Anticancer and antiviral agent. | [Description]
Introduced into therapy for the treatment of early trypanosomiasis in the 1920s, suramin, a
bis-hexasulfonatednaphthylurea, is still considered to be the drug of choice for treatment of
non-CNS-associated African trypanosomiasis. | [Definition]
ChEBI: Suramin sodium is an organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness. It has a role as an antinematodal drug, a trypanocidal drug, an antineoplastic agent, an angiogenesis inhibitor, an apoptosis inhibitor, an EC 2.7.11.13 (protein kinase C) inhibitor, a GABA antagonist, a GABA-gated chloride channel antagonist, a purinergic receptor P2 antagonist and a ryanodine receptor agonist. It contains a suramin(6-). | [Antimicrobial activity]
Suramin has no significant trypanocidal activity in vitro, but
is effective in animals infected with T. brucei. Trypanosomes
take up suramin bound to plasma protein by a combination
of fluid phase and receptor-mediated endocytosis. It acts
synergistically with nitroimidazoles and eflornithine in the
elimination of trypanosomes from CSF of infected mice. | [Acquired resistance]
Relapse rates of 30–50% have been recorded in Kenya and
Tanzania but there is no evidence of resistant parasites. Stable
resistance has been described in the related camel parasite
Trypanosoma evansi. | [Pharmaceutical Applications]
A complex symmetrical molecule originally developed in
Germany in the early 1920s for the treatment of African trypanosomiasis.
Its useful anthelmintic activity is restricted to
O. volvulus and it has been used to achieve a radical cure of
onchocerciasis by killing the adult worms. However, it is an
extremely toxic drug and its use has become increasingly
uncommon since ivermectin became available. | [Pharmaceutical Applications]
A sulfated naphthylamine formulated for intravenous administration.
It is freely soluble in water. The dry powder is stable,
but it is hygroscopic and unstable in solution. | [Mechanism of action]
Suramin is not absorbed from the intestinal tract
and is administered intravenously. Although the initial
high plasma levels drop rapidly, suramin binds tightly to
and is slowly released from plasma proteins, and so it
persists in the host for up to 3 months. Suramin neither
penetrates red blood cells nor enters the CNS. It is
taken up by the reticuloendothelial cells and accumulates
in the Kupffer cells of the liver and in the epithelial
cells of the proximal convoluted tubules of the kidney.
It is excreted by glomerular filtration, largely as the
intact molecule. | [Pharmacokinetics]
Oral absorption: Poor
Cmax 1 g intravenous doses (6 doses
at weekly intervals):
100 mg/L
Plasma half-life: 44–54 days
Volume of distribution: 20–80 L
Plasma protein binding: >99%
It is normally administered by slow intravenous infusion. It can
be detected in blood for 3 months; plasma levels >100 mg/L
were observed for several weeks after a 6-week course of treatment.
No metabolism was observed and 80% was removed
by renal clearance. Distribution to mononuclear phagocytes,
especially liver macrophages, the adrenal glands and the kidney
is high. It does not enter erythrocytes and penetrates the
blood–brain barrier poorly. | [Clinical Use]
African sleeping sickness (early stage before CNS involvement)
Onchocerciasis | [Clinical Use]
Suramin is used primarily to treat African trypanosomiasis,
for which it is the drug of choice. It is effective
in treating disease caused by Trypanosoma gambiense
and T. rhodesiense but not T. cruzi (Chagas’
disease). It can be used alone prophylactically or during
the initial hemolymphatic stages of the disease. Later
stages, particularly those involving the CNS, are more
commonly treated with a combination of suramin and
the arsenical melarsoprol.
When CNS involvement occurs, the poor penetration
of suramin and pentamidine into the CSF requires
alternative forms of chemotherapy, such as melarsoprol
in combination with suramin. In treating Onchocerca
volvulus infections, suramin kills adult worms and is an
alternative to ivermectin. Suramin is used after initial
treatment with diethylcarbamazine, which is used to kill
the microfilariae. It produces favorable results in pemphigus
and prolongs the time to disease progression in
hormone-refractory prostate cancer. | [Clinical Use]
Suramin sodium is a high molecular-weight bisurea derivative containing six sulfonic acid groups as their sodium salts. It was developed in Germany shortly after World War I as a byproduct of research efforts directed toward the development of potential antiparasitic agents from dyestuffs. The drug has been used for more than half a century for the treatment of early cases of trypanosomiasis. Not until several decades later, however, was suramin discovered to be a long-term prophylactic agent whose effectiveness after a single intravenous injection is maintained for up to 3 months. The drug is tightly bound to plasma proteins, causing its excretion in the urine to be almost negligible. Tissue penetration of the drug does not occur, apparently because of its high molecular weight and highly ionic character. Thus, an injected dose remains in the plasma for a very long period. Newer, more effective drugs are now available for short-term treatment and prophylaxis of African sleeping sickness. Suramin is also used for prophylaxis of onchocerciasis. It is available from the CDC. | [Synthesis]
Suramin, a hexasodium salt of [8,8?ˉ carbonyl-bis-[imino-3,1-phenylencarbonylimino(4-methyl-3,1-phenylen)carbonylimino]]-bis-1,3,5-naphthalintrisulfonic
acid (37.4.13), can be made by reacting 1-aminonaphthalene-3,6,8-trisulfonic acid with
4-methyl-3-nitrobenzoyl chloride to make a nitrobenzoic derivative (37.4.8). The nitro
group in this compound is reduced by activated iron to an amino derivative (37.4.9),
which is acylated by m-nitrobenzoylchloride to make a new nitroderivative, m-nitrobenzoyl-(4-methyl-3-aminobenzoyl)-1-aminonaphthalene-3,6,8-trisulfonic acid (37.4.10).
This is once again reduced to the amine (37.4.11) in the same manner. Reacting the
resulting product with phosgene makes [8,8??-carbonyl-bis-[imino-3,1-phenylencarbonylimino(4-methyl-3,1-phenylen]-carbonylimino]-bis-1,3,5-naphthalenetrisulfonic
acid (37.4.12), which upon being treated with sodium hydroxide gives suramin.
|
| Questions And Answer | Back Directory | [Pharmacology and mechanism of action]
Suramin is a polysulphonated naphthylurea introduced in Germany in 1920 for the treatment of trypanosomiasis. The drug was later found to be an effective macrofilaricide in onchocerciasis. Today suramin is mainly used for the treatment of African trypanosomiasis. It is effective against early-stages of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense without CNS involvement. However, in the case of Trypanosoma brucei gambiense pentamidine is generally preferred [1].
The mechanism of action of suramin is unknown. The drug has a broad spectrum of enzymatic actions, which is mainly due to its strong affinity for proteins. It interferes with the DNA-RNA replication mechanism of the cell, thus stopping cell growth. In vitro, suramin slowly inhibits the oxygen consumption of trypanosomes [1, 2]. In Brugia pahangi, the drug acts on the surface of the intestinal epithelium resulting in ultrastructural changes[3]. Suramin also impairs the in vitro infectivity of human immunodeficiency virus type I (HIV) [4], but the drug had little success in patients with AIDS and with different types of cancer [4, 5].
| [Indications]
Suramin is used in the treatment of early-stage infections of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. It is used prior to melarsoprol treatment to clear the blood and lymph of trypanosomes. Pentamidine is generally preferred for the treatment of early-stage Trypanosoma brucei gambiense.
Suramin is also the only drug available for effectively eliminating the adult filariae (macrofilariae) in onchocerciasis. It should only be used in individual cases.
| [Side effects]
Suramin is a toxic drug, and adverse reactions can be serious especially in malnourished patients [1]. They are also more frequently observed in patients with onchocerciasis than in patients with trypanosomiasis. Adverse reactions due to suramin can be classified into three types:
1. Immediate reactions: with a frequency of about 0.1–0.3%. These include nausea, vomiting and loss of consciousness. Slight fever, acute urticaria and colic pain are other acute reactions. These reactions can be avoided by a slow i.v. injection. It is a general clinical practice to start with a small test dose to assess the patients tolerance.
2. Late reactions (3–48 hours after i.v. injection): these include fever up to 40°C, photophobia and lacrimation. Flatulence, constipation and hyperaesthesia in the palms of the hands and the soles of the feet which can last for weeks.
3. Delayed reactions: these include kidney damage, which can occur several days after treatment and is a result of drug accumulation in the epithelial cells of the proximal convoluted tubules. Other delayed toxic reactions include dermatitis, stomatitis of theexfoliative type, agranulocytosis, haemolytic anaemia, jaundice and severe diarrhoea which may be fatal.
During onchocerciasis treatment, reactions such as urticaria, itching, formation of deep abscesses and muscle pains are common which are due to the dying worm. Nodulectomy prior to suramin therapy decreases the severity of this reaction. These reactions should be treated with 1 mg of betamethasone (equivalent to 6 mg of prednisolone) 3 times daily for 3 days[1].
| [Contraindications and precautions]
Suramin is a toxic drug and it should always be administered under medical supervision. Great caution should be exercised in malnourished patients and those with kidney diseases. Therapy should be discontinued or postponed in patients with heavy albuminuria with casts[1].
| [Interactions]
There have been no reports.
| [Preparations]
• Suramin® (Bayer). Substance for injection 1 g.
• Germanin® (Bayer). Substance for injection 1 g.
| [References]
1. Hawking, F (1978). Suramin: with special reference to onchocerciasis. Adv Pharmacol Ther, 15, 289–322.
2. Fairlamb AH, Bowman IBR (1980). Uptake of the trypanocidal drug suramin by blood stream forms of Trypanosoma brucei and its effect on respiration and growth rate in vivo. Mol Biochem Parasitol, 1, 315–333.
3. Howells RE, Mendis AM, Bray PG (1983). The mode of action of suramin on filarial worm Brugia pahangi. Parasitology, 87, 29–48.
4. Broder S, Yarchoan R, Collins JM, Lane HC, Markham PD, Klecher RW, Redfield RR, Mitsuya H, Hoth DF, German E (1985). Effects of suramin on HTLV-III/LAV infection presenting as Kaposi’s sarcoma or AIDS-related complex: clinical pharmacology and suppression of virus replication in vivo. Lancet, ii, 627–630.
5. Stein CA, LaRocca RV, Thomas R, McAtee N, Myers CE (1989). Suramin: an anticancer drug with a unique mechanism of action. J Clin Oncol, 7, 499–508.
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